Journal articles on the topic 'Vaccine candidate protein'
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Panda, Chinmaya, and Rajani Kanta Mahapatra. "Identification of novel therapeutic candidates inCryptosporidium parvum: anin silicoapproach." Parasitology 145, no. 14 (April 25, 2018): 1907–16. http://dx.doi.org/10.1017/s0031182018000677.
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AbstractUnavailability of vaccines and effective drugs are primarily responsible for the growing menace of cryptosporidiosis. This study has incorporated a bioinformatics-based screening approach to explore potential vaccine candidates and novel drug targets inCryptosporidium parvumproteome. A systematic strategy was defined for comparative genomics, orthology with relatedCryptosporidiumspecies, prioritization parameters and MHC class I and II binding promiscuity. The approach reported cytoplasmic protein cgd7_1830, a signal peptide protein, as a novel drug target. SWISS-MODEL online server was used to generate the 3D model of the protein and was validated by PROCHECK. The model has been subjected toin silicodocking study with screened potent lead compounds from the ZINC database, PubChem and ChEMBL database using Flare software package of Cresset®. Furthermore, the approach reported protein cgd3_1400, as a vaccine candidate. The predicted B- and T-cell epitopes on the proposed vaccine candidate with highest scores were also subjected to docking study with MHC class I and II alleles using ClusPro web server. Results from this study could facilitate selection of proteins which could serve as drug targets and vaccine candidates to efficiently tackle the growing threat of cryptosporidiosis.
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Zeb, Samia, Amjad Ali, Sardar Muhammad Gulfam, and Habib Bokhari. "Preliminary Work Towards Finding Proteins as Potential Vaccine Candidates for Vibrio cholerae Pakistani Isolates through Reverse Vaccinology." Medicina 55, no. 5 (May 23, 2019): 195. http://dx.doi.org/10.3390/medicina55050195.
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Background and Objective: Vibrio cholerae continues to emerge as a dangerous pathogen because of increasing resistance to a number of antibiotics. This paper provides a solution to emerging antibiotic resistance by introducing novel proteins as vaccine candidates against cholera. Materials and Methods: Vibrio cholerae genome versatility is a hurdle for developing a vaccine to combat diarrhoeal infection, so its core gene information was used to determine a potential vaccine candidate. Whole genome sequence data of more than 100 Vibrio cholerae strains were used simultaneously to get core genome information. The VacSol pipeline based on reverse vaccinology was selected to address the problem of safe, cheap, temperature-stable, and effective vaccine candidates which can be used for vaccine development against Vibrio cholerae. VacSol screens vaccine candidates using integrated, well-known, and robust algorithms/tools for proteome analysis. The proteomes of the pathogens were initially screened to predict homology using BLASTp. Proteomes that are non-homologous to humans are then subjected to a predictor for localization. Helicer predicts transmembrane helices for the protein. Proteins failing to comply with the set parameters were filtered at each step, and finally, 11 proteins were filtered as vaccine candidates. Results: This selected group of vaccine candidates consists of proteins from almost all structural parts of Vibrio cholerae. Their blast results show that this filtered group includes flagellin A protein, a protein from the Zn transporter system, a lipocarrier outer membrane protein, a peptidoglycan-associated protein, a DNA-binding protein, a chemotaxis protein, a tRNA Pseuriudine synthase A, and two selected proteins, which were beta lactamases. The last two uncharacterized proteins possess 100% similarity to V. albensis and Enterobacter, respectively. Tertiary structure and active site determination show a large number of pockets on each protein. Conclusions: The most interesting finding of this study is that 10 proteins out of 11 filtered proteins are introduced as novel potential vaccine candidates. These novel vaccine candidates can result in the development of cost-effective and broad-spectrum vaccines which can be used in countries where cholera is a major contributor to diarrheal disease.
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Tumban, Ebenezer. "Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval." Viruses 13, no. 1 (December 31, 2020): 54. http://dx.doi.org/10.3390/v13010054.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines targeting the spike protein are currently being developed to prevent against infections. Approximately 44 SARS-CoV-2 candidate vaccines are in clinical trials (phase I–III) and an additional 164 candidates are in preclinical stages. The efficacy data from phase I/II trials of lead candidate vaccines look very promising with virus-neutralizing geometric mean antibody titers in the range of 16.6–3906. Most recently, two SARS-CoV-2 candidate vaccines, BNT162b2 and mRNA-1273, have been granted the first emergency use authorization (EUA) in the U.S.; BNT162b2 has also been granted an EUA in the United Kingdom, Canada, and in the European Union. This review assesses whether SARS-CoV-2 candidate vaccines (with approved EUA or in phase III trials) meet the criteria for an ideal SARS-CoV-2 vaccine. The review concludes with expectations from phase III trials and recommendations for phase IV studies (post-vaccine approval).
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Mayers, Carl, Melanie Duffield, Sonya Rowe, Julie Miller, Bryan Lingard, Sarah Hayward, and Richard W. Titball. "Analysis of Known Bacterial Protein Vaccine Antigens Reveals Biased Physical Properties and Amino Acid Composition." Comparative and Functional Genomics 4, no. 5 (2003): 468–78. http://dx.doi.org/10.1002/cfg.319.
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Many vaccines have been developed from live attenuated forms of bacterial pathogens or from killed bacterial cells. However, an increased awareness of the potential for transient side-effects following vaccination has prompted an increased emphasis on the use of sub-unit vaccines, rather than those based on whole bacterial cells. The identification of vaccine sub-units is often a lengthy process and bioinformatics approaches have recently been used to identify candidate protein vaccine antigens. Such methods ultimately offer the promise of a more rapid advance towards preclinical studies with vaccines. We have compared the properties of known bacterial vaccine antigens against randomly selected proteins and identified differences in the make-up of these two groups. A computer algorithm that exploits these differences allows the identification of potential vaccine antigen candidates from pathogenic bacteria on the basis of their amino acid composition, a property inherently associated with sub-cellular location.
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García-Basteiro, Alberto L., Quique Bassat, and Pedro L. Alonso. "APPROACHING THE TARGET: THE PATH TOWARDS AN EFFECTIVE MALARIA VACCINE." Mediterranean Journal of Hematology and Infectious Diseases 4, no. 1 (March 10, 2012): e2012015. http://dx.doi.org/10.4084/mjhid.2012.015.
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Eliciting an effective malaria vaccine has been the goal of the scientific community for many years. A malaria vaccine, added to existing tools and strategies, would further prevent and decrease the unacceptable malaria morbidity and mortality burden. Great progress has been made over the last decade, with some vaccine candidates in the clinical phases of development. The RTS,S malaria vaccine candidate, based on a recombinant P. falciparum protein, is the most advanced of such candidates, currently undergoing a large phase III trial. RTS,S has consistently shown an efficacy of around 50% against the first clinical episode of malaria, with protection in some cases extending up to 4 years of duration. Thus, it is hoped that this candidate vaccine will eventually become the first licensed malaria vaccine. This first vaccine against a human parasite is a groundbreaking achievement, but improved malaria vaccines conferring higher protection will be needed if the aspiration of malaria eradication is to be achieved
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van Doremalen, Neeltje, Robert J. Fischer, Jonathan E. Schulz, Myndi G. Holbrook, Brian J. Smith, Jamie Lovaglio, Benjamin Petsch, and Vincent J. Munster. "Immunogenicity of Low-Dose Prime-Boost Vaccination of mRNA Vaccine CV07050101 in Non-Human Primates." Viruses 13, no. 8 (August 19, 2021): 1645. http://dx.doi.org/10.3390/v13081645.
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Many different vaccine candidates against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, are currently approved and under development. Vaccine platforms vary from mRNA vaccines to viral-vectored vaccines, and several candidates have been shown to produce humoral and cellular responses in small animal models, non-human primates, and human volunteers. In this study, six non-human primates received a prime-boost intramuscular vaccination with 4 µg of mRNA vaccine candidate CV07050101, which encodes a pre-fusion stabilized spike (S) protein of SARS-CoV-2. Boost vaccination was performed 28 days post prime vaccination. As a control, six animals were similarly injected with PBS. Humoral and cellular immune responses were investigated at time of vaccination, and two weeks afterwards. No antibodies could be detected at two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in four out of six non-human primates. SARS-CoV-2 S protein-specific T cell responses were detected in these four animals. In conclusion, prime-boost vaccination with 4 µg of vaccine candidate CV07050101 resulted in limited immune responses in four out of six non-human primates.
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Loo, Ke-Yan, Vengadesh Letchumanan, Hooi-Leng Ser, Siew Li Teoh, Jodi Woan-Fei Law, Loh Teng-Hern Tan, Nurul-Syakima Ab Mutalib, Kok-Gan Chan, and Learn-Han Lee. "COVID-19: Insights into Potential Vaccines." Microorganisms 9, no. 3 (March 15, 2021): 605. http://dx.doi.org/10.3390/microorganisms9030605.
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People around the world ushered in the new year 2021 with a fear of COVID-19, as family members have lost their loved ones to the disease. Millions of people have been infected, and the livelihood of many has been jeopardized due to the pandemic. Pharmaceutical companies are racing against time to develop an effective vaccine to protect against COVID-19. Researchers have developed various types of candidate vaccines with the release of the genetic sequence of the SARS-CoV-2 virus in January. These include inactivated viral vaccines, protein subunit vaccines, mRNA vaccines, and recombinant viral vector vaccines. To date, several vaccines have been authorized for emergency use and they have been administered in countries across the globe. Meanwhile, there are also vaccine candidates in Phase III clinical trials awaiting results and approval from authorities. These candidates have shown positive results in the previous stages of the trials, whereby they could induce an immune response with minimal side effects in the participants. This review aims to discuss the different vaccine platforms and the clinical trials of the candidate vaccines.
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Wainwright, Eleanor, and Rebecca K. Shears. "Trichuris WAP and CAP proteins: Potential whipworm vaccine candidates?" PLOS Neglected Tropical Diseases 16, no. 12 (December 22, 2022): e0010933. http://dx.doi.org/10.1371/journal.pntd.0010933.
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Trichuris trichiura and T. suis are gastrointestinal dwelling roundworms that infect humans and pigs, respectively. Heavy infections cause gastrointestinal symptoms and impaired growth and development. Vaccination has the potential to reduce the disease burden of whipworm infection; however, there are currently no commercially available vaccines against these parasites and very few against other gastrointestinal-dwelling nematodes of medical and agricultural importance. The naturally occurring mouse whipworm, T. muris, has been used for decades to model human trichuriasis, and the immunogenic potential of the excretory/secretory material (E/S, which can be collected following ex vivo culture of worms) has been studied in the context of vaccine candidate identification. Despite this, researchers are yet to progress an effective vaccine candidate to clinical trials. The T. muris, T. trichiura, and T. suis genomes each encode between 10 and 27 whey acidic protein (WAP) domain-containing proteins and 15 to 34 cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) family members. WAP and CAP proteins have been postulated to play key roles in host–parasite interactions and may possess immunomodulatory functions. In addition, both protein families have been explored in the context of helminth vaccines. Here, we use phylogenetic and functional analysis to investigate the evolutionary relationship between WAP and CAP proteins encoded by T. muris, T. trichiura, and T. suis. We highlight several WAP and CAP proteins that warrant further study to understand their biological function and as possible vaccine candidates against T. trichiura and/or T. suis, based on the close evolutionary relationship with WAP or CAP proteins identified within T. muris E/S products.
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Schautteet, Katelijn, Edith Stuyven, Eric Cox, and Daisy Vanrompay. "Validation of the Chlamydia trachomatis genital challenge pig model for testing recombinant protein vaccines." Journal of Medical Microbiology 60, no. 1 (January 1, 2011): 117–27. http://dx.doi.org/10.1099/jmm.0.024448-0.
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Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen that is the leading cause of bacterial sexually transmitted disease in humans in developing countries. A vaccination programme is considered to be the best approach to reduce the prevalence of C. trachomatis infections. However, there are still no commercial C. trachomatis vaccines. In order to develop effective C. trachomatis vaccines, it is important to identify those antigens that elicit a protective immune response, and to develop new and adequate methods and adjuvants for effective vaccine delivery, as conventional methods have failed to induce protective immunity. In order to test different vaccine candidates, animal models are needed. Former studies have used non-primate monkeys, mice or guinea pig infection models. The present study used a pig model for testing recombinant protein vaccines. Two recombinant proteins, polymorphic membrane protein G (PmpG), and secretion and cellular translocation protein C (SctC), were tested for their ability to create protection in a pig C. trachomatis challenge model. The vaccines were administered subcutaneously with GNE adjuvant. Six weeks later, animals were challenged intravaginally with C. trachomatis serovar E. After a further 4 weeks, the pigs were euthanized. PmpG-immunized pigs were better protected than pigs immunized with the less promising SctC candidate vaccine antigen. Interestingly, significant protection was apparently not correlated with a strong humoral immune response upon subcutaneous immunization. In conclusion, the pig model is useful for studying the efficacy of vaccine candidates against genital human C. trachomatis infection.
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Wattimena, Mauritz Nicolaas, and Wijanarka Wijanarka. "In Silico Analysis Prediction of B-Cell Epitope as a Vaccine Candidate for SARS-CoV-2 B.1.617.2 (Delta) Variant." Journal of Biomedicine and Translational Research 1, no. 1 (March 8, 2022): 7–15. http://dx.doi.org/10.14710/jbtr.v1i1.13113.
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Background: The COVID-19 pandemic by SARS-CoV-2 has caused many losses. One way to prevent the spread of this virus is to get vaccinated. However, the latest SARS-CoV-2 variants, including variant B.1.617.2 (Delta) are doubtful to be inhibited by existing vaccines because of mutations. Therefore, we need a new vaccine candidate that is effective against this SARS-CoV-2 variant. Through an immunoinformatics approach with various software and analysis websites, vaccine candidates can be predicted in a short time.Objective: Identity, analyze, obtain, and confirm the selected B-cell epitope sequence that can be used as a vaccine candidate for the SARS-CoV-2 B.1.617.2 (Delta) variant.Methods: This research was conducted by isolating the amino acid peptide sequence in the SARS-CoV-2 B.1.617.2 (Delta) variant protein spike from the Protein Data Bank which is suspected to be an immunogenic epitope and can be used as a vaccine candidate. A Series of tests were carried out such as antigenicity, toxicity, allergenicity, and BLAST® protein to ensure that this vaccine candidate is safe for later application into the human body. The next stage is a conservation analysis to see its potential by comparing it with the SARS-CoV-2 Delta (B.1.617.2) variant spike protein sequence in Indonesia. The study ended by mapping amino acid peptides to the SARS-CoV-2 Delta (B.1.617.2) variant spike protein using the Biovia Discovery Studio Visualizer v21.1.0.20298 2020 software to ensure that the selected sequences were epitope.Results: From the five amino acid peptides that have been isolated, the FTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFT epitope sequence has good results than the others. It is probable an antigen, non-toxic, non-allergen, and non-homolog to the human body protein.Conclusion: Based on this in silico study, it was found that the FTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFT epitope sequence was the best to be used as a vaccine candidate of SARS-CoV-2 B.1.617.2 (Delta) variant.Keywords: SARS-CoV-2 B.1.617.2 (Delta) variant, B-cell epitope, vaccine, in silico, immunoinformatics.
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Hong, So-Hee, Hanseul Oh, Yong Wook Park, Hye Won Kwak, Eun Young Oh, Hyo-Jung Park, Kyung Won Kang, et al. "Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates." Science Advances 7, no. 22 (May 2021): eabg7156. http://dx.doi.org/10.1126/sciadv.abg7156.
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Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.
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Monterrubio-López, Gloria P., Jorge A. González-Y-Merchand, and Rosa María Ribas-Aparicio. "Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology." BioMed Research International 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/483150.
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Tuberculosis (TB) is a chronic infectious disease, considered as the second leading cause of death worldwide, caused byMycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG) vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens byin silicoapproaches.M. tuberculosisH37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment) prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, fromM. tuberculosisthat can be used to improve or design new TB vaccines.
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Bellamkonda, Navya, Upendra Pradeep Lambe, Sonali Sawant, Shyam Sundar Nandi, Chiranjib Chakraborty, and Deepak Shukla. "Immune Response to SARS-CoV-2 Vaccines." Biomedicines 10, no. 7 (June 21, 2022): 1464. http://dx.doi.org/10.3390/biomedicines10071464.
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COVID-19 vaccines have been developed to confer immunity against the SARS-CoV-2 infection. Prior to the pandemic of COVID-19 which started in March 2020, there was a well-established understanding about the structure and pathogenesis of previously known Coronaviruses from the SARS and MERS outbreaks. In addition to this, vaccines for various Coronaviruses were available for veterinary use. This knowledge supported the creation of various vaccine platforms for SARS-CoV-2. Before COVID-19 there are no reports of a vaccine being developed in under a year and no vaccine for preventing coronavirus infection in humans had ever been developed. Approximately nine different technologies are being researched and developed at various levels in order to design an effective COVID-19 vaccine. As the spike protein of SARS-CoV-2 is responsible for generating substantial adaptive immune response, mostly all the vaccine candidates have been targeting the whole spike protein or epitopes of spike protein as a vaccine candidate. In this review, we have compiled the immune response to SARS-CoV-2 infection and followed by the mechanism of action of various vaccine platforms such as mRNA vaccines, Adenoviral vectored vaccine, inactivated virus vaccines and subunit vaccines in the market. In the end we have also summarized the various adjuvants used in the COVID-19 vaccine formulation.
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Hudson, Laura C., Renu Garg, Kenneth L. Bost, and Kenneth J. Piller. "Soybean Seeds: A Practical Host for the Production of Functional Subunit Vaccines." BioMed Research International 2014 (2014): 1–13. http://dx.doi.org/10.1155/2014/340804.
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Soybean seeds possess several inherent qualities that make them an ideal host for the production of biopharmaceuticals when compared with other plant-based and non-plant-based recombinant expression systems (e.g., low cost of production, high protein to biomass ratio, long-term stability of seed proteins under ambient conditions, etc.). To demonstrate the practicality and feasibility of this platform for the production of subunit vaccines, we chose to express and characterize a nontoxic form ofS. aureusenterotoxin B (mSEB) as a model vaccine candidate. We show that soy-mSEB was produced at a high vaccine to biomass ratio and represented ~76 theoretical doses of human vaccine per single soybean seed. We localized the model vaccine candidate both intracellularly and extracellularly and found no difference in mSEB protein stability or accumulation relative to subcellular environment. We also show that the model vaccine was biochemically and immunologically similar to native and recombinant forms of the protein produced in a bacterial expression system. Immunization of mice with seed extracts containing mSEB mounted a significant immune response within 14 days of the first injection. Taken together, our results highlight the practicality of soybean seeds as a potential platform for the production of functional subunit vaccines.
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Brown, Jeremy S., A. David Ogunniyi, Matthew C. Woodrow, David W. Holden, and James C. Paton. "Immunization with Components of Two Iron Uptake ABC Transporters Protects Mice against Systemic Streptococcus pneumoniae Infection." Infection and Immunity 69, no. 11 (November 1, 2001): 6702–6. http://dx.doi.org/10.1128/iai.69.11.6702-6706.2001.
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ABSTRACT There has been considerable recent research into protein basedStreptococcus pneumoniae vaccines as alternatives to the existing capsular antigen vaccines. PiuA and PiaA (formerly Pit1A and Pit2A) are recently identified lipoprotein components of S. pneumoniae iron uptake ABC transporters which are required for full virulence and are likely to be expressed on the surface of the bacterial cell membrane. We investigated the efficacy of recombinant PiuA and PiaA proteins at eliciting protective immunity in mice against systemic infection with S. pneumoniae. Both recombinant PiuA and PiaA generated antibody responses that cross-reacted with each other but not with pneumolysin and reacted with identical proteins from nine different S. pneumoniae serotypes. Mice immunized with recombinant PiuA and PiaA were protected against systemic challenge to a degree similar to those immunized with an existing protein vaccine candidate, PdB (a genetically modified pneumolysin toxoid). Immunization with a combination of both PiuA and PiaA resulted in additive protection and was highly protective against systemic infection with S. pneumoniae. PiuA and PiaA are therefore promising additional candidates for a novel S. pneumoniae vaccine using protein antigens.
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Chathuranga, W. A. Gayan, Chamith Hewawaduge, N. A. Nadeeka Nethmini, Tae-Hwan Kim, Ju Hun Kim, Young-Hoon Ahn, In-Joong Yoon, Sung-Sik Yoo, Jong-Hyeon Park, and Jong-Soo Lee. "Efficacy of a Novel Multiepitope Vaccine Candidate against Foot-and-Mouth Disease Virus Serotype O and A." Vaccines 10, no. 12 (December 19, 2022): 2181. http://dx.doi.org/10.3390/vaccines10122181.
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Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease in cloven-hoofed animals. To prevent the spread of FMD virus (FMDV), traditional inactivated vaccines are used to immunize susceptible animals in disease-endemic countries. However, the inactivated FMD vaccine has several limitations, including safety concerns. To overcome these limitations, subunit proteins have been studied as alternative vaccine candidates. In this study, we designed two multiepitope recombinant proteins (OVM and AVM) containing antigenic sites (residue of VP1 132–162 and residue of VP1 192–212) of three topotypes of FMDV serotype O or three topotypes of FMDV serotype A. Each recombinant protein was efficiently expressed in Escherichia coli with high solubility, and the immunogenicity and protective efficacy of the proteins as FMD vaccine candidates were evaluated. The results showed that OVM and AVM emulsified with ISA201 adjuvant induced effective antigen-specific humoral and cell-mediated immune responses and successfully protected mice from O/Jincheon/SKR/2014, O/VET/2013, and A/Malaysia/97 viruses. In addition, intramuscular immunization of pigs with the OVM and AVM emulsified with ISA201 elicited effective levels of neutralizing antibodies to the viruses with homologous epitopes. Importantly, OVM-AVM emulsified with CAvant®SOE-X adjuvant conferred 100% protection against the O/Jincheon/SKR/2014 virus with homologous residues and 75% protection against A/SKR/GP/2018 with heterologous residues. The results presented in this study suggest that the combination of OVM and AVM protein with an effective adjuvant could yield an effective and safe vaccine candidate for the prevention and control of foot-and-mouth disease. In addition, our results provide a vaccine platform that can safely, cost-efficiently, and rapidly generate protective vaccine candidates against diverse FMDVs.
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Wang, Xingyun, Nino Rcheulishvili, Jie Cai, Cong Liu, Fengfei Xie, Xing Hu, Nuo Yang, et al. "Development of DNA Vaccine Candidate against SARS-CoV-2." Viruses 14, no. 5 (May 15, 2022): 1049. http://dx.doi.org/10.3390/v14051049.
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Despite the existence of various types of vaccines and the involvement of the world’s leading pharmaceutical companies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the most challenging health threat in this century. Along with the increased transmissibility, new strains continue to emerge leading to the need for more vaccines that would elicit protectiveness and safety against the new strains of the virus. Nucleic acid vaccines seem to be the most effective approach in case of a sudden outbreak of infection or the emergence of a new strain as it requires less time than any conventional vaccine development. Hence, in the current study, a DNA vaccine encoding the trimeric prefusion-stabilized ectodomain (S1+S2) of SARS-CoV-2 S-protein was designed by introducing six additional prolines mutation, termed HexaPro. The three-dose regimen of designed DNA vaccine immunization in mice demonstrated the generation of protective antibodies.
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Alshammari, Abdulrahman, Abdullah F. Alasmari, Metab Alharbi, Nemat Ali, Ziyad Tariq Muhseen, Usman Ali Ashfaq, Miraj Ud-din, Asad Ullah, Muhammad Arshad, and Sajjad Ahmad. "Novel Chimeric Vaccine Candidate Development against Leptotrichia buccalis." International Journal of Environmental Research and Public Health 19, no. 17 (August 29, 2022): 10742. http://dx.doi.org/10.3390/ijerph191710742.
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The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. Leptotrichia buccalis is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of −300 to −500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen.
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Matsegora, N. А., and A. V. Kaprosh. "Current state of developments and research of new candidate vaccines against tuberculosis (literature review)." Tuberculosis, Lung Diseases, HIV Infection, no. 2 (June 17, 2022): 48–57. http://dx.doi.org/10.30978/tb-2022-2-48.
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147 literature sources on Tuberculosis vaccine, Vaccine prevention of tuberculosis were considered, 33 of them were studied in detail.According to the WHO report, 14 candidates for the TB vaccine are in clinical trials, including the AEC/BC02, Ad5 Ag85A and ChAdOx185A-MVA85A phase 1 vaccines, MTBVAC, ID93+GLA-SE, TB / FLU-04L and the GamB phase vaccine. 2a, amplifiers DAR-901, H56:IC31, M72/AS01, BCG revaccination and RUTI vaccine in phase 2b, VPM1002 and MIP/Immuvac in phase 3. Candidate TB vaccines vary in type and purpose.By type of vaccine are: subunit, vector, genetically modified live recombinant vaccines, live attenuated vaccines containing M. tuberculosis, inactivated vaccines.Subunit TB vaccines — contain purified immunoactive protein components isolated from M. tuberculosis with the addition of an adjuvant to enhance their immunogenic properties.Recombinant live vaccines — use a live vector to deliver heterologous antigens that elicit an immune response.Weakened live vaccines — contain a variant of a live pathogen that has been weakened to prevent serious disease when administered.Inactivated tuberculosis vaccines are designed to prevent and treat TB and are still being studied. These are vaccines with inactivated whole bacteria or their cleavage fragments, prepared physically or chemically.According to the purpose, vaccine candidates are studied in different target groups as pre- and post-exposure prophylaxis, in the context of anti-relapse prophylaxis and therapeutic vaccination, as well as to prevent the activation of LTBI in HIV-infected and contact persons.The results of recent clinical trials are important in addressing critical knowledge gaps and will clearly demonstrate the value of new TB vaccination strategies for endemic countries, and will shape the next generation of clinical trials.
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Rostad, Christina A., Christopher C. Stobart, Brian E. Gilbert, Ray J. Pickles, Anne L. Hotard, Jia Meng, Jorge C. G. Blanco, et al. "A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats." Journal of Virology 90, no. 16 (June 8, 2016): 7508–18. http://dx.doi.org/10.1128/jvi.00012-16.
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ABSTRACTAlthough respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10total PFU and 2.7 log10PFU/g of tissue, respectively, compared to those in unvaccinated animals (P< 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity.IMPORTANCERSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats.
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Harland, David N., Karen Chu, Ashraful Haque, Michelle Nelson, Nicola J. Walker, Mitali Sarkar-Tyson, Timothy P. Atkins, et al. "Identification of a LolC Homologue in Burkholderia pseudomallei, a Novel Protective Antigen for Melioidosis." Infection and Immunity 75, no. 8 (May 21, 2007): 4173–80. http://dx.doi.org/10.1128/iai.00404-07.
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ABSTRACT Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing this disease, Burkholderia pseudomallei, is also considered a bioterrorism agent, and as yet there is no licensed vaccine for preventing B. pseudomallei infection. In this study, we evaluated selected proteins (LolC, PotF, and OppA) of the ATP-binding cassette systems of B. pseudomallei as candidate vaccine antigens. Nonmembrane regions of the B. pseudomallei proteins were expressed and purified from Escherichia coli and then evaluated as vaccine candidates in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the proteins stimulated antigen-specific humoral and cellular immune responses. Immunization with LolC or PotF protein domains afforded significant protection against a subsequent challenge with B. pseudomallei. The most promising vaccine candidate, LolC, provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also protected against a subsequent challenge with a heterologous strain of B. pseudomallei, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis.
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Huang, Claire Y. H., Siritorn Butrapet, Dennis J. Pierro, Gwong-Jen J. Chang, Ann R. Hunt, Natth Bhamarapravati, Duane J. Gubler, and Richard M. Kinney. "Chimeric Dengue Type 2 (Vaccine Strain PDK-53)/Dengue Type 1 Virus as a Potential Candidate Dengue Type 1 Virus Vaccine." Journal of Virology 74, no. 7 (April 1, 2000): 3020–28. http://dx.doi.org/10.1128/jvi.74.7.3020-3028.2000.
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ABSTRACT We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-1 16007 virus or its vaccine derivative, strain PDK-13. We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of the parental DEN-1 16007 virus retained the attenuation markers of small plaque size and temperature sensitivity in LLC-MK2 cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-1 virus than did the candidate DEN-1 PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envelope protein of DEN-1 PDK-13 virus affected in vitro phenotype and immunogenicity in mice. The current PDK-13 vaccine is the least efficient of the four Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-53 vaccine are promising attenuated vectors for development of chimeric flavivirus vaccines.
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Wang, Yan, Kui Zhao, Deguang Song, Le Du, Xinyue Wang, Feng Gao, Huijun Lu, and Jiyu Guan. "Evaluation of the Immune Response Afforded by Combined Immunization with Orf Virus DNA and Subunit Vaccine in Mice." Vaccines 10, no. 9 (September 8, 2022): 1499. http://dx.doi.org/10.3390/vaccines10091499.
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Contagious ecthyma (Orf) is a highly contagious disease caused by Orf virus (ORFV) infection. Orf is prevalent all over the world and, not only affects the healthy development of sheep husbandry, but also threatens human health. However, there are no safe and effective vaccines or drugs for the prevention and treatment of Orf at present. In this study, we constructed a DNA plasmid expressing ORFV B2L and F1L genes as a DNA vaccine candidate, with purified B2L full-length protein and F1L truncated protein as subunit vaccine candidates. BALB/c mice were immunized with the DNA vaccine, subunit vaccine, as well as DNA prime-protein boost strategies. The results showed that compared with the DNA vaccine and subunit vaccine alone, the DNA prime-protein boost immunization group had a higher level of specific antibodies, stronger lymphocyte proliferation, and higher expression of cytokines such as IL-2, IL-4, IL-6, IFN-γ, and TNF-α, which are considered to cause a Th1/Th2 mixed cytokine response. Our results demonstrated that the DNA prime-protein boost immunization strategy induced stronger humoral and cellular immune responses, which have potential advantages in preventing ORFV infection.
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Eroshkin, Alexey M., Elena A. Karginova, Irina P. Gileva, Alexander S. Lomakin, Leonid R. Lebedev, Tatiana P. Kamyinina, Alexander V. Pereboev, and Georgy M. Ignat'ev. "Design of four-helix bundle protein as a candidate for HIV vaccine." "Protein Engineering, Design and Selection" 8, no. 2 (1995): 167–73. http://dx.doi.org/10.1093/protein/8.2.167.
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Võ, Tuấn-Cường, Haung Naw, Rochelle A. Flores, Hương-Giang Lê, Jung-Mi Kang, Won-Gi Yoo, Woo-Hyun Kim, Wongi Min, and Byoung-Kuk Na. "Genetic Diversity of Microneme Protein 2 and Surface Antigen 1 of Eimeria tenella." Genes 12, no. 9 (September 15, 2021): 1418. http://dx.doi.org/10.3390/genes12091418.
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Avian coccidiosis is a disease caused by members of the genus Eimeria. Huge economic losses incurred by the global poultry industry due to coccidiosis have increased the need for cost-effective and easily available recombinant vaccines. Microneme protein 2 (MIC2) and surface antigen 1 (SAG1) of E. tenella have been recognised as potential vaccine candidates. However, the genetic diversity of the antigens in field isolates, which affects vaccine efficacy, has yet to be largely investigated. Here, we analysed genetic diversity and natural selection of etmic2 and etsag1 in Korean E. tenella isolates. Both genes exhibited low levels of genetic diversity in Korean isolates. However, the two genes showed different patterns of nucleotide diversity and amino acid polymorphism involving the E. tenella isolates obtained from different countries including China and India. These results underscore the need to investigate the genetic diversity of the vaccine candidate antigens and warrant monitoring of genetic heterogeneity and evolutionary aspects of the genes in larger numbers of E. tenella field isolates from different geographical areas to design effective coccidial vaccines.
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Naung, Myo T., Elijah Martin, Jacob Munro, Somya Mehra, Andrew J. Guy, Moses Laman, G. L. Abby Harrison, et al. "Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens." PLOS Computational Biology 18, no. 2 (February 2, 2022): e1009801. http://dx.doi.org/10.1371/journal.pcbi.1009801.
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Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene ‘haplotypes’ from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines.
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Murawski, Matthew R., Lori W. McGinnes, Robert W. Finberg, Evelyn A. Kurt-Jones, Michael J. Massare, Gale Smith, Penny M. Heaton, Armando E. Fraire, and Trudy G. Morrison. "Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology." Journal of Virology 84, no. 2 (November 4, 2009): 1110–23. http://dx.doi.org/10.1128/jvi.01709-09.
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ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 μg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G-immunized mice, no enhanced pathology in the lungs was observed, although lungs of mice immunized in parallel with formalin-inactivated RSV (FI-RSV) showed the significant pathology that has previously been documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs, with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for protection against RSV.
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Venkatesan, Malabi M. "A novel protein‐based subunit Shigella vaccine candidate." Immunology & Cell Biology 93, no. 7 (June 9, 2015): 603–4. http://dx.doi.org/10.1038/icb.2015.56.
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Bystrický, S. "Candida albicans mannan–protein conjugate as vaccine candidate." Immunology Letters 85, no. 3 (February 3, 2003): 251–55. http://dx.doi.org/10.1016/s0165-2478(02)00241-9.
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Davila, Jose, Lixin Zhang, Carl F. Marrs, Riza Durmaz, and Zhenhua Yang. "Assessment of the Genetic Diversity ofMycobacterium tuberculosis esxA, esxH, andfbpBGenes among Clinical Isolates and Its Implication for the Future Immunization by New Tuberculosis Subunit Vaccines Ag85B-ESAT-6 and Ag85B-TB10.4." Journal of Biomedicine and Biotechnology 2010 (2010): 1–6. http://dx.doi.org/10.1155/2010/208371.
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The effort to develop a tuberculosis (TB) vaccine more effective than the widely used Bacille Calmette-Guérin (BCG) has led to the development of two novel fusion protein subunit vaccines: Ag85B-ESAT-6 and Ag85B-TB10.4. Studies of these vaccines in animal models have revealed their ability to generate protective immune responses. Yet, previous work on TB fusion subunit vaccine candidate, Mtb72f, has suggested that genetic diversity amongM. tuberculosisstrains may compromise vaccine efficacy. In this study, we sequenced theesxA, esxH,andfbpBgenes ofM. tuberculosisencoding ESAT-6, TB10.4, and Ag85B proteins, respectively, in a sample of 88 clinical isolates representing 57 strains from Ark, USA, and 31 strains from Turkey, to assess the genetic diversity of the two vaccine candidates. We found no DNA polymorphism inesxAandesxHgenes in the study sample and only one synonymous single nucleotide change (C to A) infbpBgene among 39 (44.3%) of the 88 strains sequenced. These data suggest that it is unlikely that the efficacy of Ag85B-ESAT-6 and Ag85B-TB10.4 vaccines will be affected by the genetic diversity ofM. tuberculosispopulation. Future studies should include a broader pool ofM. tuberculosisstrains to validate the current conclusion.
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Ouattara, Amed, Anki Dwivedit, Matthew Adams, Amadou Niangaly, Matthew B. Laurens, Myaing M. Nyunt, Christopher V. Plowe, Abdoulaye Djimde, Shannon Takala-Harrison, and Joana C. Silva. "An In Silico Analysis of Malaria Pre-Erythrocytic-Stage Antigens Interpreting Worldwide Genetic Data to Suggest Vaccine Candidate Variants and Epitopes." Microorganisms 10, no. 6 (May 25, 2022): 1090. http://dx.doi.org/10.3390/microorganisms10061090.
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Failure to account for genetic diversity of antigens during vaccine design may lead to vaccine escape. To evaluate the vaccine escape potential of antigens used in vaccines currently in development or clinical testing, we surveyed the genetic diversity, measured population differentiation, and performed in silico prediction and analysis of T-cell epitopes of ten such Plasmodium falciparum pre-erythrocytic-stage antigens using whole-genome sequence data from 1010 field isolates. Of these, 699 were collected in Africa (Burkina Faso, Cameroon, Guinea, Kenya, Malawi, Mali, and Tanzania), 69 in South America (Brazil, Colombia, French Guiana, and Peru), 59 in Oceania (Papua New Guinea), and 183 in Asia (Cambodia, Myanmar, and Thailand). Antigens surveyed include cell-traversal protein for ookinetes and sporozoites, circumsporozoite protein, liver-stage antigens 1 and 3, sporozoite surface proteins P36 and P52, sporozoite asparagine-rich protein-1, sporozoite microneme protein essential for cell traversal-2, and upregulated-in-infectious-sporozoite 3 and 4 proteins. The analyses showed that a limited number of these protein variants, when combined, would be representative of worldwide parasite populations. Moreover, predicted T-cell epitopes were identified that could be further explored for immunogenicity and protective efficacy. Findings can inform the rational design of a multivalent malaria vaccine.
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Song, Xingju, Xu Yang, Taotao Zhang, Jing Liu, and Qun Liu. "A Novel Rhoptry Protein as Candidate Vaccine against Eimeria tenella Infection." Vaccines 8, no. 3 (August 12, 2020): 452. http://dx.doi.org/10.3390/vaccines8030452.
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Eimeria tenella (E. tenella) is a highly pathogenic and prevalent species of Eimeria that infects chickens, and it causes a considerable disease burden worldwide. The secreted proteins and surface antigens of E. tenella at the sporozoite stage play an essential role in the host–parasite interaction, which involves attachment and invasion, and these interactions are considered vaccine candidates based on the strategy of cutting off the invasion pathway to interrupt infection. We selected two highly expressed surface antigens (SAGs; Et-SAG13 and Et-SAG) and two highly expressed secreted antigens (rhoptry kinases Eten5-A, Et-ROPK-Eten5-A and dense granule 12, Et-GRA12) at the sporozoite stage. Et-ROPK-Eten5-A and Et-GRA12 were two unexplored proteins. Et-ROPK-Eten5-A was an E. tenella-specific rhoptry (ROP) protein and distributed in the apical pole of sporozoites and merozoites. Et-GRA12 was scattered in granular form at the sporozoite stage. To evaluate the potential of rEt-ROPK-Eten5-A, rEt-GRA12, rEt-SAG13 and rEt-SAG proteins as a coccidiosis vaccine, the protective efficacy was examined based on survival rate, lesion score, body weight gain, relative body weight gain and oocyst output. The survival rate was significantly improved in rEt-ROPK-Eten5-A (100%) and rEt-GRA12 (100%) immune chickens compared to the challenged control group (40%). The average body weight gains of rEt-ROPK-Eten5-A, rEt-GRA12, rEt-SAG13 and rEt-SAG immunized chickens were significantly higher than those of unimmunized chickens. The mean lesion score and oocyst output of the rEt-ROPK-Eten5-A immunized chickens were significantly reduced compared to unimmunized challenged chickens. These results suggest that the rEt-ROPK-Eten5-A protein effectively triggered protection against E. tenella in chickens and provides a useful foundation for future work developing anticoccidial vaccines.
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Zhao, Ping, Jin-Shan Ke, Zhao-Lin Qin, Hao Ren, Lan-Juan Zhao, Jian-Guo Yu, Jun Gao, Shi-Ying Zhu, and Zhong-Tian Qi. "DNA Vaccine of SARS-Cov S Gene Induces Antibody Response in Mice." Acta Biochimica et Biophysica Sinica 36, no. 1 (January 1, 2004): 37–41. http://dx.doi.org/10.1093/abbs/36.1.37.
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Abstract The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is one of the most important antigen candidates for vaccine design. In the present study, three fragments of the truncated S protein were expressed in E. coli, and analyzed with pooled sera of convalescence phase of SARS patients. The full length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The mouse serum IgG antibody against SARS-CoV was measured by ELISA with E. coli expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The results showed that all the three fragments of S protein expressed by E. coli was able to react with sera of SARS patients and the S gene DNA candidate vaccine could induce the production of specific IgG antibody against SARS-CoV efficiently in mice with seroconversion ratio of 75% after 3 times of immunization. These findings lay some foundations for further understanding the immunology of SARS-CoV and developing SARS vaccines.
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Varyushina, Elena A., Georgy V. Alexandrov, Mikhail S. Zakharov, Anna S. Kiryanova, Olga E. Huttunen, Alina B. Rumyantseva, Ilya D. Mitrofanov, et al. "Study of immunogenicity and safety of a candidate rotavirus vaccine based on a recombinant hybrid protein." Medical academic journal 21, no. 2 (September 24, 2021): 87–98. http://dx.doi.org/10.17816/maj71134.
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BACKGROUND: Rotaviruses are the main cause of acute gastroenteritis in children in both developed and developing countries. Vaccination is the only way to prevent severe and fatal course of this disease. Live attenuated viruses-based vaccines currently available can have a number of side effects. A candidate rotavirus vaccine reported is based on a hybrid recombinant protein FliCVP6VP8, which includes a VP6 protein fragment, a rotavirus A VP8 protein fragment, and S. typhimurium FliC flagellin components.
AIM: The aim was to evaluate the immunogenicity and safety of а preparation Rotavirus vaccine, recombinant in preclinical studies.
MATERIALS AND METHODS: The immunogenicity of vaccine (blood antibody titers, antigen-specific proliferative response of spleen cells) was evaluated in BALB/c mice. The acute and subchronic toxicity, the possible irritating effect, pyrogenicity and the anaphylactic effect and delayed type hypersensitivity were evaluated in laboratory mice, rats, Guinea pigs, and rabbits.
RESULTS: Double immunization of mice with the candidate vaccine demonstrated a significant increase in antibody titers in mouse sera compared to that in control mice. Evaluation of antigen-specific proliferative response after double immunization with a candidate vaccine demonstrated a significant increase in the values of stimulated proliferation. Evaluation of safety through acute and chronic toxicity studies demonstrated no toxicity. The immunostimulatory effect of vaccine was demonstrated when evaluating the number of antibody-producing cells with sheep red blood cells as antigens. The number of white blood cells was demonstrated to increase after the prolonged vaccine administration.
CONCLUSIONS: The preclinical studies have demonstrated safety of the candidate rotavirus vaccine and its capability to produce the immune response.
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Alshabrmi, Fahad M., Faris Alrumaihi, Sahar Falah Alrasheedi, Wafa Abdullah I. Al-Megrin, Ahmad Almatroudi, and Khaled S. Allemailem. "An In-Silico Investigation to Design a Multi-Epitopes Vaccine against Multi-Drug Resistant Hafnia alvei." Vaccines 10, no. 7 (July 15, 2022): 1127. http://dx.doi.org/10.3390/vaccines10071127.
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Antimicrobial resistance has become a significant health issue because of the misuse of antibiotics in our daily lives, resulting in high rates of morbidity and mortality. Hafnia alvei is a rod-shaped, Gram-negative and facultative anaerobic bacteria. The medical community has emphasized H. alvei’s possible association with gastroenteritis. As of now, there is no licensed vaccine for H. alvei, and as such, computer aided vaccine design approaches could be an ideal approach to highlight the potential vaccine epitopes against this bacteria. By using bacterial pan-genome analysis (BPGA), we were able to study the entire proteomes of H. alvei with the aim of developing a vaccine. Based on the analysis, 20,370 proteins were identified as core proteins, which were further used in identifying potential vaccine targets based on several vaccine candidacy parameters. The prioritized vaccine targets against the bacteria are; type 1 fimbrial protein, flagellar hook length control protein (FliK), flagellar hook associated protein (FlgK), curli production assembly/transport protein (CsgF), fimbria/pilus outer membrane usher protein, fimbria/pilus outer membrane usher protein, molecular chaperone, flagellar filament capping protein (FliD), TonB-dependent hemoglobin /transferrin/lactoferrin family receptor, Porin (OmpA), flagellar basal body rod protein (FlgF) and flagellar hook-basal body complex protein (FliE). During the epitope prediction phase, different antigenic, immunogenic, non-Allergenic, and non-Toxic epitopes were predicted for the above-mentioned proteins. The selected epitopes were combined to generate a multi-epitope vaccine construct and a cholera toxin B subunit (adjuvant) was added to enhance the vaccine’s antigenicity. Downward analyses of vaccines were performed using a vaccine three-dimensional model. Docking studies have confirmed that the vaccine strongly binds with MHC-I, MHC-II, and TLR-4 immune cell receptors. Additionally, molecular dynamics simulations confirmed that the vaccine epitopes were exposed to nature and to the host immune system and interpreted strong intermolecular binding between the vaccine and receptors. Based on the results of the study, the model vaccine construct seems to have the capacity to produce protective immune responses in the host, making it an attractive candidate for further in vitro and in vivo studies.
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Tsybalova, L. M., L. A. Stepanova, M. A. Shuklina, S. V. Petrov, A. A. Kovaleva, M. V. Potapchuk, A. A. Shaldzhan, Y. A. Zabrodskaya, and V. V. Egorov. "CROSS-PROTECTIVE PROPERTIES OF AN INFLUENZA VACCINE BASED ON HBC4M2E RECOMBINANT PROTEIN." Problems of Virology, Russian journal 63, no. 2 (April 20, 2018): 68–76. http://dx.doi.org/10.18821/0507-4088-2018-63-2-68-76.
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One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.
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Warner, Nikole L., and Kathryn M. Frietze. "Development of Bacteriophage Virus-Like Particle Vaccines Displaying Conserved Epitopes of Dengue Virus Non-Structural Protein 1." Vaccines 9, no. 7 (July 2, 2021): 726. http://dx.doi.org/10.3390/vaccines9070726.
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Dengue virus (DENV) is a major global health problem, with over half of the world’s population at risk of infection. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Here, we describe efforts to engineer epitope-based vaccines against DENV non-structural protein 1 (NS1). NS1 is present in DENV-infected cells as well as secreted into the blood of infected individuals. NS1 causes disruption of endothelial cell barriers, resulting in plasma leakage and hemorrhage. Immunizing against NS1 could elicit antibodies that block NS1 function and also target NS1-infected cells for antibody-dependent cell cytotoxicity. We identified highly conserved regions of NS1 from all four DENV serotypes. We generated synthetic peptides to these regions and chemically conjugated them to bacteriophage Qβ virus-like particles (VLPs). Mice were immunized two times with the candidate vaccines and sera were tested for the presence of antibodies that bound to the cognate peptide, recombinant NS1 from all four DENV serotypes, and DENV-2-infected cells. We found that two of the candidate vaccines elicited antibodies that bound to recombinant NS1, and one candidate vaccine elicited antibodies that bound to DENV-infected cells. These results show that an epitope-specific vaccine against conserved regions of NS1 could be a promising approach for DENV vaccines or therapeutics to bind circulating NS1 protein.
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Ismail, Saba, Noorah Alsowayeh, Hyder Wajid Abbasi, Aqel Albutti, Muhammad Tahir ul Qamar, Sajjad Ahmad, Rabail Zehra Raza, Khulah Sadia, and Sumra Wajid Abbasi. "Pan-Genome-Assisted Computational Design of a Multi-Epitopes-Based Vaccine Candidate against Helicobacter cinaedi." International Journal of Environmental Research and Public Health 19, no. 18 (September 14, 2022): 11579. http://dx.doi.org/10.3390/ijerph191811579.
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Helicobacter cinaedi is a Gram-negative bacterium from the family Helicobacteraceae and genus Helicobacter. The pathogen is a causative agent of gastroenteritis, cellulitis, and bacteremia. The increasing antibiotic resistance pattern of the pathogen prompts the efforts to develop a vaccine to prevent dissemination of the bacteria and stop the spread of antibiotic resistance (AR) determinants. Herein, a pan-genome analysis of the pathogen strains was performed to shed light on its core genome and its exploration for potential vaccine targets. In total, four vaccine candidates (TonB dependent receptor, flagellar hook protein FlgE, Hcp family type VI secretion system effector, flagellar motor protein MotB) were identified as promising vaccine candidates and subsequently subjected to an epitopes’ mapping phase. These vaccine candidates are part of the pathogen core genome: they are essential, localized at the pathogen surface, and are antigenic. Immunoinformatics was further applied on the selected vaccine proteins to predict potential antigenic, non-allergic, non-toxic, virulent, and DRB*0101 epitopes. The selected epitopes were then fused using linkers to structure a multi-epitopes’ vaccine construct. Molecular docking simulations were conducted to determine a designed vaccine binding stability with TLR5 innate immune receptor. Further, binding free energy by MMGB/PBSA and WaterSwap was employed to examine atomic level interaction energies. The designed vaccine also stimulated strong humoral and cellular immune responses as well as interferon and cytokines’ production. In a nutshell, the designed vaccine is promising in terms of immune responses’ stimulation and could be an ideal candidate for experimental analysis due to favorable physicochemical properties.
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Green, Bruce A., Ying Zhang, Amy W. Masi, Vicki Barniak, Michael Wetherell, Robert P. Smith, Molakala S. Reddy, and Duzhang Zhu. "PppA, a Surface-Exposed Protein of Streptococcus pneumoniae, Elicits Cross-Reactive Antibodies That Reduce Colonization in a Murine Intranasal Immunization and Challenge Model." Infection and Immunity 73, no. 2 (February 2005): 981–89. http://dx.doi.org/10.1128/iai.73.2.981-989.2005.
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ABSTRACT The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due to Streptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins from S. pneumoniae that may be involved in pathogenesis to test as vaccine candidates. Here, an ∼20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein from Listeria innocua and other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains of S. pneumoniae and were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologous S. pneumoniae type 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.
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Ragan, Izabela K., Lindsay M. Hartson, Taru S. Dutt, Andres Obregon-Henao, Rachel M. Maison, Paul Gordy, Amy Fox, et al. "A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model." Vaccines 9, no. 4 (April 1, 2021): 340. http://dx.doi.org/10.3390/vaccines9040340.
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The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.
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Liu, Xinsheng, Donghong Zhao, Peng Zhou, Yongguang Zhang, and Yonglu Wang. "Evaluation of the Efficacy of a Recombinant Adenovirus Expressing the Spike Protein of Porcine Epidemic Diarrhea Virus in Pigs." BioMed Research International 2019 (October 8, 2019): 1–8. http://dx.doi.org/10.1155/2019/8530273.
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In recent years, many studies have shown that recombinant adenovirus live vector-based vaccines are a promising novel vaccine candidate against virus infection. Therefore, in this study, a new type of recombinant adenovirus expressing the spike (S) protein of porcine epidemic diarrhea virus (PEDV), rAd-PEDV-S, was generated, and its characteristics were determined. Then, its efficacy as a vaccine candidate was evaluated in 4-week-old pigs. The results showed that the S protein could be well expressed at a high level in rAd-PEDV-S-infected cells and that the viral titers could reach 1011 PFU/mL. Further animal experimental results showed that rAd-PEDV-S elicited a significant PEDV-specific humoral immune response after vaccination (P<0.05). In addition, rAd-PEDV-S provided partial protection for pigs against the highly virulent PEDV challenge. The results presented in this study indicate that the adenovirus vector can be used as a vaccine delivery vector for the development of a PEDV vaccine and is a promising novel vaccine candidate for future prevention and control of porcine epidemic diarrhea (PED), but its efficacy still needs to be improved in the future.
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Moezzi, Maryam Sadat, Abdollah Derakhshandeh, and Farhid Hemmatzadeh. "Immunoinformatics analysis of candidate proteins for controlling bovine paratuberculosis." PLOS ONE 17, no. 11 (November 21, 2022): e0277751. http://dx.doi.org/10.1371/journal.pone.0277751.
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Background Paratuberculosis is debilitating chronic enteritis usually characterized by diarrhea, decreased milk production, and progressive cachexia. Mycobacterium avium subspecies paratuberculosis (MAP) causes significant economic losses by affecting dairy herds globally. Development of protective vaccines is considered as one of the most effective controlling measures for MAP infections. In the current study, hydrophilic parts of MAP2191 and FAP-P proteins as two vaccine candidates were analyzed using immunoinformatics approaches. Methods After selecting the most hydrophilic parts of MAP2191 and FAP-P, helper and cytotoxic T-cell epitopes of ht-MAP2191 and ht-FAP-P were identified. The immunogenic, toxicity and physicochemical properties were assessed. Secondary structures of these proteins were predicted, and their tertiary structures were modeled, refined, and validated. Linear and conformational epitopes of corresponding B-cells were recognized. Then ht-MAP2191 and ht-FAP-P epitopes were employed for molecular docking simulations. Results The results indicated that ht-MAP2191 and ht-FAP-P were immunogenic, non-allergenic, and non-toxic and possess potent T-cell and B-cell epitopes. Eventually, these protein constructs were docked favorably against TLR4. Conclusion According to the findings, ht-MAP2191 and ht-FAP-P could be effective protein-based vaccine candidates for paratuberculosis. It should be noted that to examine their efficacy, further in vitro and in vivo experiments are underway.
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Anand, S. B., K. N. Kodumudi, M. V. Reddy, and P. Kaliraj. "A combination of two Brugia malayi filarial vaccine candidate antigens (BmALT-2 and BmVAH) enhances immune responses and protection in jirds." Journal of Helminthology 85, no. 4 (January 4, 2011): 442–52. http://dx.doi.org/10.1017/s0022149x10000799.
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AbstractIn this study filarial recombinant protein or DNA vaccine constructs encoding BmALT-2 and BmVAH as single or as cocktail antigens were evaluated. Male jirds were immunized intramuscularly with DNA vaccine constructs or were immunized intraperitoneally with protein vaccine. The single and bicistronic DNA constructs induced substantial interferon-γ responses in spleen cells; antigen-specific responses were higher following immunization with the bicistronic cocktail construct and evoked a significant protective response of 57% in jirds challenged with Brugia malayi that was similar in the antibody-dependent cellular cytotoxicity (ADCC) assay and micropore chamber experiment. The cocktail protein vaccines induced a mixture of IgG2a (Th1) and IgG1 (Th2) responses with 80% protective response when challenged with B. malayi infective larvae. However, the single protein vaccine rALT-2 induced Th2 (IgG1/IgG3) with a 70% protective response and rVAH induced Th1 (IgG2a) with a lower proliferative response with 60% protection following challenge with B. malayi infective larvae. These results suggest that filarial cocktail protein vaccines are able to elicit substantial immune and protective responses when compared with single antigen vaccination in suitably vaccinated jirds.
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Tang, Tian, Chuan Wang, Qikang Pu, Jinmei Peng, Sijing Liu, Chenyan Ren, Mingjuan Jiang, and Zhijun Tian. "Vaccination of Mice with Listeria ivanovii Expressing the Truncated M Protein of Porcine Reproductive and Respiratory Syndrome Virus Induces both Antigen-Specific CD4+ and CD8+ T Cell-Mediated Immunity." Journal of Molecular Microbiology and Biotechnology 29, no. 1-6 (2019): 74–82. http://dx.doi.org/10.1159/000506686.
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Porcine reproductive and respiratory syndrome (PRRS), a serious disease of swine caused by the PRRS virus (PRRSV), had a severe economic impact worldwide. As commonly used PRRS vaccines, the attenuated or inactivated vaccines, provide unsatisfactory immune protection, a new PRRS vaccine is urgently needed. In this study, a part of the PRRSV <i>ORF6</i> gene (from 253 to 519 bp) encoding the hydrophilic domain of PRRSV M protein was integrated into two <i>Listeria</i> strains via homologous recombination to generate two PRRS vaccine candidates, namely LI-M’ and LM-Δ<i>actAplcB</i>-M’. Both candidate vaccines showed similar growth rate as their parent strains in culture media, but presented different bacterial loads in target organs. As the integrated heterogenous gene was not expressed, LM-Δ<i>actAplcB</i>-M’ was excluded from the immunological test. In a mouse model, LI-M’ provoked both CD4+ and CD8+ T cell-mediated immunity. In addition, LI-M’ boosting dramatically enhanced CD8+ T cell-mediated immunity without affecting the response intensity of CD4+ T cell-mediated immunity. All of these data suggest that LI-M’ is a promising PRRS vaccine candidate.
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Li, Entao, Feihu Yan, Pei Huang, Hang Chi, Shengnan Xu, Guohua Li, Chuanyu Liu, et al. "Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice." Viruses 12, no. 1 (January 20, 2020): 125. http://dx.doi.org/10.3390/v12010125.
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Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.
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Royal, Joshua M., Carrie A. Simpson, Alison A. McCormick, Amanda Phillips, Steve Hume, Josh Morton, John Shepherd, et al. "Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle." Vaccines 9, no. 11 (November 17, 2021): 1347. http://dx.doi.org/10.3390/vaccines9111347.
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Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.
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Chen, Edwin, Nichole D. Salinas, Yining Huang, Francis Ntumngia, Manolo D. Plasencia, Michael L. Gross, John H. Adams, and Niraj Harish Tolia. "Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein." Proceedings of the National Academy of Sciences 113, no. 22 (May 18, 2016): 6277–82. http://dx.doi.org/10.1073/pnas.1600488113.
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Plasmodium vivax Duffy Binding Protein (PvDBP) is the most promising vaccine candidate for P. vivax malaria. The polymorphic nature of PvDBP induces strain-specific immune responses, however, and the epitopes of broadly neutralizing antibodies are unknown. These features hamper the rational design of potent DBP-based vaccines and necessitate the identification of globally conserved epitopes. Using X-ray crystallography, small-angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry, and mutational mapping, we have defined epitopes for three inhibitory mAbs (mAbs 2D10, 2H2, and 2C6) and one noninhibitory mAb (3D10) that engage DBP. These studies expand the currently known inhibitory epitope repertoire by establishing protective motifs in subdomain three outside the receptor-binding and dimerization residues of DBP, and introduce globally conserved protective targets. All of the epitopes are highly conserved among DBP alleles. The identification of broadly conserved epitopes of inhibitory antibodies provides critical motifs that should be retained in the next generation of potent vaccines for P. vivax malaria.
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Lamazares, Emilio, Fernando Gutiérrez, Angela Hidalgo, Nicolas A. Gutiérrez, Felipe I. Espinoza, Oliberto Sánchez, Marcelo Cortez-San Martín, et al. "A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate." Viruses 12, no. 4 (March 31, 2020): 385. http://dx.doi.org/10.3390/v12040385.
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Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.
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Beernink, Peter T., and Dan M. Granoff. "Bactericidal Antibody Responses Induced by Meningococcal Recombinant Chimeric Factor H-Binding Protein Vaccines." Infection and Immunity 76, no. 6 (March 24, 2008): 2568–75. http://dx.doi.org/10.1128/iai.00033-08.
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ABSTRACT Factor H-binding protein (fHbp) is a novel meningococcal vaccine candidate that elicits serum antibodies that activate classical complement pathway bacteriolysis and also inhibit binding of the complement down-regulatory protein, factor H, to the bacterial surface. One limitation of fHbp as a vaccine candidate is antigenic variability, since antibodies to fHbp in the variant 1 (v.1) antigenic group do not protect against strains expressing v.2 or v.3 proteins, and vice versa. We have identified amino acid residues of epitopes recognized by bactericidal anti-fHbp monoclonal antibodies prepared against fHbp from each of the variant groups. One epitope expressed by nearly all v.1 proteins mapped to the B domain, while epitopes expressed by fHbp v.2 or v.3 mapped to the C domain. The results provided the rationale for engineering chimeric fHbp molecules containing the A domain (which is conserved across all variant groups), a portion of the B domain of a v.1 protein, and the carboxyl-terminal portion of the B domain and the C domain of a v.2 protein. By enzyme-linked immunosorbent assay, the resulting recombinant chimeric proteins expressed epitopes from all three variant groups. In mice, the chimeric vaccines elicited serum antibodies with bactericidal activity against a panel of genetically diverse strains expressing fHbp v.1, v.2, or v.3. The data demonstrate the feasibility of preparing a meningococcal vaccine from a single recombinant protein that elicits broad bactericidal activity, including group B strains, which account for 50 percent of cases of meningococcal disease and for which there currently is no broadly protective vaccine.
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Jahantigh, Hamid Reza, Angela Stufano, Farhad Koohpeyma, Vajihe Sadat Nikbin, Zahra Shahosseini, and Piero Lovreglio. "Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice." Vaccines 11, no. 1 (January 3, 2023): 115. http://dx.doi.org/10.3390/vaccines11010115.
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The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.