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1

van Diepen, Michiel, Rosamund Chapman, Nicola Douglass, Leah Whittle, Nicole Chineka, Shireen Galant, Christian Cotchobos, Akiko Suzuki, and Anna-Lise Williamson. "Advancements in the Growth and Construction of Recombinant Lumpy Skin Disease Virus (LSDV) for Use as a Vaccine Vector." Vaccines 9, no. 10 (October 4, 2021): 1131. http://dx.doi.org/10.3390/vaccines9101131.

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Attenuated vaccine strains of lumpy skin disease virus (LSDV) have become increasingly popular as recombinant vaccine vectors, to target both LSDV, as well as other pathogens, including human infectious agents. Historically, these vaccine strains and recombinants were generated in primary (lamb) testis (LT) cells, Madin–Darby bovine kidney (MDBK) cells or in eggs. Growth in eggs is a laborious process, the use of primary cells has the potential to introduce pathogens and MDBK cells are known to harbor bovine viral diarrhea virus (BVDV). In this study, data is presented to show the growth of an attenuated LSDV strain in baby hamster kidney (BHK-21) cells. Subsequently, a recombinant LSDV vaccine was generated in BHK-21 cells. Partial growth was also observed in rabbit kidney cells (RK13), but only when the vaccinia virus host range gene K1L was expressed. Despite the limited growth, the expression of K1L was enough to serve as a positive selection marker for the generation of recombinant LSDV vaccines in RK13 cells. The simplification of generating (recombinant) LSDV vaccines shown here should increase the interest for this platform for future livestock vaccine development and, with BHK-21 cells approved for current good manufacturing practice, this can be expanded to human vaccines as well.
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Cuervo, Nancy Stella, Sophie Guillot, Natalia Romanenkova, Mariana Combiescu, André Aubert-Combiescu, Mohamed Seghier, Valérie Caro, Radu Crainic, and Francis Delpeyroux. "Genomic Features of Intertypic Recombinant Sabin Poliovirus Strains Excreted by Primary Vaccinees." Journal of Virology 75, no. 13 (July 1, 2001): 5740–51. http://dx.doi.org/10.1128/jvi.75.13.5740-5751.2001.

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ABSTRACT The trivalent oral poliomyelitis vaccine (OPV) contains three different poliovirus serotypes. It use therefore creates particularly favorable conditions for mixed infection of gut cells, and indeed intertypic vaccine-derived recombinants (VdRec) have been frequently found in patients with vaccine-associated paralytic poliomyelitis. Nevertheless, there have not been extensive searches for VdRec in healthy vaccinees following immunization with OPV. To determine the incidence of VdRec and their excretion kinetics in primary vaccinees, and to establish the general genomic features of the corresponding recombinant genomes, we characterized poliovirus isolates excreted by vaccinees following primary immunization with OPV. Isolates were collected from 67 children 2 to 60 days following vaccination. Recombinant strains were identified by multiple restriction fragment length polymorphism assays. The localization of junction sites in recombinant genomes was also determined. VdRec excreted by vaccinees were first detected 2 to 4 days after vaccination. The highest rate of recombinants was on day 14. The frequency of VdRec depends strongly on the serotype of the analyzed isolates (2, 53, and 79% of recombinant strains in the last-excreted type 1, 2, and 3 isolates, respectively). Particular associations of genomic segments were preferred in the recombinant genomes, and recombination junctions were found in the genomic region encoding the nonstructural proteins. Recombination junctions generally clustered in particular subgenomic regions that were dependent on the serotype of the isolate and/or on the associations of genomic segments in recombinants. Thus, VdRec are frequently excreted by vaccinees, and the poliovirus replication machinery requirements or selection factors appear to act in vivo to shape the features of the recombinant genomes.
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Ertl, H. C., and Z. Xiang. "Novel vaccine approaches." Journal of Immunology 156, no. 10 (May 15, 1996): 3579–82. http://dx.doi.org/10.4049/jimmunol.156.10.3579.

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Abstract Recent advances in immunology, molecular biology, and peptide biochemistry have allowed the construction of subunit vaccines based on viral or bacterial recombinants, peptides or plasmid vectors. Although none of these approaches is currently being used for mass vaccination (with the exception or vaccinia-rabies G protein recombinant virus for wildlife immunization); several of them are undergoing clinical trials. None of these different vaccine constructs is likely to be totally effective in either the prevention of infectious diseases or immunotherapy of cancer. Recombinant viral vaccines such as those based on vaccinia or adenovirus as a rule induce potent immune responses. Vaccinia viruses have the added advantage of being heat stable and immunogenic after oral application, making them good candidates for wildlife immunization. Recombinants based on replication-defective adenoviruses are safer compared with vaccinia virus recombinants and, as far as our data indicate, have superior efficacy. In addition, they induce excellent immunity upon application to mucosal membranes, suggesting their usefulness as vaccines for infectious agents that enter through the airways or the genital tract. Peptides are of limited benefit in infectious disease prevention but might provide custom-made vaccines for cancer therapy. Genetic vaccines that were first described less than 5 years ago have already progressed to phase I clinical trials in healthy human adults. Provided that their safety can be confirmed, they might be suited to induce immunity to numerous agents.
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Marra, Yasmin, and Fawziah Lalji. "Prevention of Herpes Zoster: A Focus on the Effectiveness and Safety of Herpes Zoster Vaccines." Viruses 14, no. 12 (November 29, 2022): 2667. http://dx.doi.org/10.3390/v14122667.

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Infection with varicella zoster virus typically occurs in children and it can cause primary varicella infection or “chickenpox”, or it can reactivate later in life and cause herpes zoster or “shingles”. Herpes zoster mainly occurs in older adults, causing a reduction in activities of daily living, impacting quality of life, and may lead to serious complications, including chronic pain. Two vaccines are marketed to prevent herpes zoster: the live zoster vaccine and the non-live, recombinant zoster vaccine. The pre-licensure clinical trials show the efficacy of the live zoster vaccine to be between 50 and 70% and for the recombinant vaccine to be higher at 90 to 97%. Real-world effectiveness studies, with a follow-up of approximately 10 years, were reviewed in this article. These data corroborated the efficacy studies, with vaccine effectiveness being 46% and 85% for the live and recombinant vaccines, respectively. Safety data from the effectiveness studies show similar results to the clinical trials with mostly local injection-site reactions and mild systemic reactions seen with both vaccines, although in larger proportions with the recombinant vaccine. Rare adverse events, occurring less than 1% of the time, have been seen with both vaccine types and include disseminated herpes zoster with the live zoster vaccine and Guillain–Barré syndrome with the recombinant vaccine. The wider use of preventative measures with vaccines will reduce the herpes zoster burden of illness seen in older adults.
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5

Hudu, Shuaibu Abdullahi, Saadatu Haruna Shinkafi, and Shuaibu Umar. "AN OVERVIEW OF RECOMBINANT VACCINE TECHNOLOGY, ADJUVANTS AND VACCINE DELIVERY METHODS." International Journal of Pharmacy and Pharmaceutical Sciences 8, no. 11 (October 28, 2016): 19. http://dx.doi.org/10.22159/ijpps.2016v8i11.14311.

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Development of an effective vaccine is of paramount important in disease prevention and control. As such, recombinant technology can serve as a gateway for the development of safe and effective vaccines that can be delivered effectively with an appropriate adjuvant. Therefore, this paper aimed to review the role of recombinant vaccine technology, new adjuvants and the challenge of vaccine delivery. Related peer-reviewed journal article searches were conducted using a subscribed database at the Universiti Putra Malaysia library, involving areas of Health Sciences and Medicine via Medline, SCOPUS and Google Scholar. New generation vaccines include highly purified synthetic or recombinant antigens that stimulate effective cell-mediated immune and mucosal immunity. In order to enhance their efficacy, a number of adjuvants are used. Efforts have also been made to explore the usage of non-invasive routes of administration, devices and equipment for optimized antigen and immune-potentiator delivery of the immune system. Recombinant vaccine technology is rapid, compared to the traditional method of vaccine development and does not require the handling of live viruses. It is, therefore, a promising technology for developing a future vaccine to curb emerging and re-emerging viral infections that may be life-threatening or teratogenic.
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6

Wu, Xiao-Xin, Hang-Ping Yao, Nan-Ping Wu, Hai-Nv Gao, Hai-Bo Wu, Chang-Zhong Jin, Xiang-Yun Lu, Tian-Shen Xie, and Lan-Juan Li. "Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease." Cellular Physiology and Biochemistry 37, no. 5 (2015): 1641–58. http://dx.doi.org/10.1159/000438531.

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Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirus∆VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.
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7

Koeberling, Oliver, Isabel Delany, and Dan M. Granoff. "A Critical Threshold of Meningococcal Factor H Binding Protein Expression Is Required for Increased Breadth of Protective Antibodies Elicited by Native Outer Membrane Vesicle Vaccines." Clinical and Vaccine Immunology 18, no. 5 (March 2, 2011): 736–42. http://dx.doi.org/10.1128/cvi.00542-10.

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ABSTRACTNative outer membrane vesicles (NOMV) (not detergent treated), which are prepared from recombinant strains with attenuated endotoxin activity and overexpressed factor H binding protein (fHbp), elicited broad serum bactericidal antibody responses in mice. The amount of overexpressed fHbp required for optimal immunogenicity is not known. In this study we prepared NOMV vaccines from LpxL1 knockout (ΔLpxL1) mutants with penta-acylated lipooligosaccharide and attenuated endotoxin activity. The recombinant strains had wild-type (1×) fHbp expression or were engineered for 3-fold- or 10-fold-increased fHbp expression (3× or 10× fHbp). Control vaccines included NOMV from ΔLpxL1/ΔfHbp mutants or recombinant fHbp. In mice, only the 10× fHbp NOMV vaccine elicited significantly higher serum IgG anti-fHbp antibody titers than the corresponding 1× fHbp NOMV or recombinant fHbp vaccine. The 10× fHbp NOMV vaccine also elicited higher bactericidal responses (P< 0.05) against five group B strains with heterologous PorA than the recombinant fHbp or 1× fHbp NOMV vaccine. The 3× fHbp NOMV vaccine gave higher bactericidal titers against only one strain. Serum bactericidal titers in mice immunized with the control ΔfHbp NOMV vaccines were <1:10, and bactericidal titers in mice immunized with the 10× fHbp NOMV vaccine were <1:10 after adsorption of anti-fHbp antibodies. Mixing antiserum to NOMV vaccines from fHbp knockout mutants with antiserum to recombinant fHbp did not increase anti-fHbp bactericidal titers. Thus, a critical threshold of increased fHbp expression is required for NOMV vaccines to elicit broad serum bactericidal responses, and the antibodies conferring protection are directed primarily at fHbp.
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8

Schlom, Jeffrey. "Recombinant cancer vaccines and new vaccine targets." Expert Review of Vaccines 12, no. 10 (October 2013): 1121–24. http://dx.doi.org/10.1586/14760584.2013.836913.

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9

Stover, C. Kendall. "Recombinant vaccine delivery systems and encoded vaccines." Current Opinion in Immunology 6, no. 4 (August 1994): 568–71. http://dx.doi.org/10.1016/0952-7915(94)90143-0.

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10

Dewidar, Abdelmonem A. A., Walid H. Kilany, Azza A. El-Sawah, Salama A. S. Shany, Al-Hussien M. Dahshan, Islam Hisham, Magdy F. Elkady, and Ahmed Ali. "Genotype VII.1.1-Based Newcastle Disease Virus Vaccines Afford Better Protection against Field Isolates in Commercial Broiler Chickens." Animals 12, no. 13 (June 30, 2022): 1696. http://dx.doi.org/10.3390/ani12131696.

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This study evaluated the efficacy of live and inactivated conventional GII LaSota and recombinant GVII Newcastle disease vaccines in commercial broilers. The experimental groups (G2–G7) were vaccinated on day 7 and day 21 of age with live vaccines from the same vaccine type “GII LaSota, GVII vaccine (A), GVII vaccine (B)” via eye drop; however, G3, G5, and G7 received a single dose from inactivated counterpart vaccines subcutaneously on day 7 of age. Vaccine efficacy was evaluated based on elicited humoral immunity, clinical protection, and reduction in virus shedding after challenge with virulent GVII 1.1. strain. Results demonstrated that live and inactivated recombinant GVII vaccine based on VG/GA strain backbone elicited superior protection parameters (100% protection). Although the conventional GII LaSota live and inactivated vaccination regime protected 93.3% of vaccinated birds, the virus shedding continued until 10 DPC. The post-vaccination serological monitoring was consistent with protection results. The study concludes that conventional GII ND vaccines alone are probably insufficient due to the current epidemiology of the GVII 1.1 NDV strains. Our findings further support that protection induced by recombinant GVII 1.1. ND vaccines are superior. Interestingly, the efficacy of recombinant ND vaccines seemed to be influenced by the backbone virus since the VG/GA backbone-based vaccine provided better protection and reduced virus shedding.
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11

Baldo, Aline, Amaya Leunda, Nicolas Willemarck, and Katia Pauwels. "Environmental Risk Assessment of Recombinant Viral Vector Vaccines against SARS-Cov-2." Vaccines 9, no. 5 (May 3, 2021): 453. http://dx.doi.org/10.3390/vaccines9050453.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Over the past months, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Various platforms are being used for the development of COVID-19 vaccine candidates: recombinant viral vectors, protein-based vaccines, nucleic acid-based vaccines, and inactivated/attenuated virus. Recombinant viral vector vaccine candidates represent a significant part of those vaccine candidates in clinical development, with two already authorised for use in the European Union and one currently under rolling review by the European Medicines Agency (EMA). Since recombinant viral vector vaccine candidates are considered as genetically modified organisms (GMOs), their regulatory oversight includes besides an assessment of their quality, safety and efficacy, also an environmental risk assessment (ERA). The present article highlights the main characteristics of recombinant viral vector vaccine (candidates) against SARS-CoV-2 in the pipeline and discusses their features from an environmental risk point of view.
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12

Gorse, Geoffrey J., Ramona E. Simionescu, and Gira B. Patel. "Cellular Immune Responses in Asymptomatic Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Effects of Vaccination with Recombinant Envelope Glycoprotein of HIV-1." Clinical and Vaccine Immunology 13, no. 1 (January 2006): 26–32. http://dx.doi.org/10.1128/cvi.13.1.26-32.2006.

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ABSTRACT Effects of human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein vaccines on cell-mediated immune (CMI) responses were assessed in HIV-1-infected patients. Asymptomatic, antiretroviral-treatment-naïve, HIV-1-infected patients with CD4+ T-cell counts greater than 400/μl received multiple intramuscular injections of HIV-1 IIIB recombinant envelope glycoprotein (rgp160) vaccine or HIV-1 MN recombinant envelope glycoprotein (rgp120) vaccine (eight patients, referred to as the HIV-1 vaccinees) or placebo or hepatitis B vaccine (three patients, referred to as the controls). Lymphocyte proliferation in response to HIV-1 envelope glycoproteins, both homologous and heterologous to the HIV-1 immunogens, was absent prior to study treatment in all patients but increased significantly during the vaccination series and after the final vaccination in HIV-1 vaccinees (P < 0.05) and remained absent in control patients. In flow cytometric analyses of intracellular cytokines, T-cell receptor stimulation with an anti-CD3 antibody induced gamma interferon (IFN-γ) expression by activated CD4+ and CD8+ lymphocytes at greater frequencies than did stimulation with recombinant envelope glycoprotein and p24 of HIV-1 (P< 0.05). Mean frequencies of HIV-1 envelope glycoprotein-stimulated, activated intracellularIFN-γ-producing CD4+ and CD8+ lymphocytes and of interleukin-2-producing CD4+ lymphocytes did not increase after vaccination, but cytokine-producing cells were detectable in some patients. Comparing pre- to post-HIV-1 vaccination time points, changes in frequencies of activated, IFN-γ-producing CD4+ cells correlated inversely with changes in lymphocyte proliferation in response to recombinant envelope glycoprotein in HIV-1 vaccinees (P < 0.05). Increased CMI responses to HIV-1 envelope glycoprotein measured by lymphocyte proliferation were associated with HIV-1 recombinant envelope glycoprotein vaccines.
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Weaver, Eric A. "Dose Effects of Recombinant Adenovirus Immunization in Rodents." Vaccines 7, no. 4 (October 10, 2019): 144. http://dx.doi.org/10.3390/vaccines7040144.

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Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very difficult to compare immune responses and vaccine efficacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. Rats did not show dose-dependent antibody responses to increasing vaccine doses. The IM immunized mice and rats also showed significant dose-dependent T cell responses to the rAd vaccine. However, the T cell immunity plateaued in both mice and rats at 109 and 1010 vp/animal, respectively. Additionally, the highest dose of vaccine in mice and rats did not improve the T cell responses. A final vaccine analysis using a lethal influenza virus challenge showed that despite the differences in the immune responses observed in the mice, the mice had very similar patterns of protection. This indicates that rAd vaccines induced dose-dependent immune responses, especially in IM immunized animals, and that immune correlates are not as predictive of protection as initially thought.
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Shollenberger, Lisa, Rafaella Grenfell, E. Farah Samli, and Donald Harn. "Vaccine self-assembling immune matrix (VacSIM) is a non-viral delivery platform that augments responses to recombinant protein vaccines (VAC6P.940)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 140.1. http://dx.doi.org/10.4049/jimmunol.192.supp.140.1.

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Abstract Vaccination remains the most effective public health tool to prevent infectious disease. However, many vaccines remain marginally effective, especially for immune-compromised populations. To enhance vaccine immunogenicity, we exploited the biphasic property of certain synthetic oligopeptides to create a new vaccine delivery method, VacSIM (vaccine self-assembling immune matrix). Vaccine components are easily mixed with the VacSIM solution for injection, after which the peptides self-assemble into hydrated nanofiber gel-matrices, forming a vaccine depot. Thus, we have a non-viral, inert, biodegradable delivery system, not requiring formulation, which we can use to deliver a multitude of vaccines. Analogous to a treat-dispensing dog toy, VacSIM is a carrier for vaccine components, allowing for gradual release, rather than immediate administration. We believe this depot attracts antigen presenting cells, driving enhanced vaccine-specific responses that improve both the quantity and quality of the response. We have tested this delivery platform with live bacterial vectors, inactivated virus and multiple recombinant protein vaccines. Shown here, VacSIM augments vaccine responses to the recombinant Hepatitis B surface antigen and recombinant HIV Envelope in 2 strains of mice. Enhancement of vaccine responses by VacSIM administration could represent a fundamental paradigm shift in how vaccines are delivered.
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Hongying, Fan, Wu Xianbo, Yu Fang, Bai Yang, and Long Beiguo. "Oral Immunization with Recombinant Lactobacillus acidophilus Expressing the Adhesin Hp0410 of Helicobacter pylori Induces Mucosal and Systemic Immune Responses." Clinical and Vaccine Immunology 21, no. 2 (November 27, 2013): 126–32. http://dx.doi.org/10.1128/cvi.00434-13.

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ABSTRACTHelicobacter pyloriinfection is relatively common worldwide and is closely related to gastric mucosa-associated lymphoid tissue (MALT) lymphoma, chronic gastritis, and stomach ulcers. Therefore, a safe and effective method for preventingH. pyloriinfection is urgently needed. Given that developing an effective vaccine againstH. pyloriis one of the best alternatives,H. pyloriadhesin Hp0410 was expressed in the food-grade bacteriumLactobacillus acidophilus. The recombinant live bacterial vaccine was then used to orally vaccinate mice, and the immunoprotective effects of Hp0410-producing strains were investigated.H. pyloricolonization in the stomach of mice immunized with the recombinantL. acidophiluswas significantly reduced, in comparison with that in control groups. Furthermore, mucosal secretory IgA antibodies were elicited in the mucosal tissue of mice immunized with the recombinant bacteria, and specific anti-Hp0410 IgG responses were also detected in mouse serum. There was a significant increase in the level of protection against gastricHelicobacterinfection following a challenge withH. pyloriSydney strain 1 (SS1). Our results collectively indicate that adhesin Hp0410 is a promising candidate vaccine antigen, and recombinantL. acidophilusexpressing Hp0410 is likely to constitute an effective, low-cost, live bacterial vaccine againstH. pylori.
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Yan, Lin, Jin Qiu, Jianbo Chen, Bridgett Ryan-Payseur, Dan Huang, Yunqi Wang, Lijun Rong, Jody A. Melton-Witt, Nancy E. Freitag, and Zheng W. Chen. "Selected prfA* Mutations in Recombinant Attenuated Listeria monocytogenes Strains Augment Expression of Foreign Immunogens and Enhance Vaccine-Elicited Humoral and Cellular Immune Responses." Infection and Immunity 76, no. 8 (May 12, 2008): 3439–50. http://dx.doi.org/10.1128/iai.00245-08.

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ABSTRACT While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes ΔactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes ΔactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes ΔactA vaccine vector. Thus, recombinant attenuated L. monocytogenes ΔactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.
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Chang, Pengxiang, Faisal Ameen, Joshua E. Sealy, Jean-Remy Sadeyen, Sushant Bhat, Yongqing Li, and Munir Iqbal. "Application of HDR-CRISPR/Cas9 and Erythrocyte Binding for Rapid Generation of Recombinant Turkey Herpesvirus-Vectored Avian Influenza Virus Vaccines." Vaccines 7, no. 4 (November 22, 2019): 192. http://dx.doi.org/10.3390/vaccines7040192.

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Avian influenza viruses (AIVs) are highly contagious and have caused huge economical loss to the poultry industry. AIV vaccines remain one of the most effective methods of controlling this disease. Turkey herpesvirus (HVT) is a commonly used live attenuated vaccine against Marek’s disease; it has also been used as a viral vector for recombinant AIV vaccine development. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system is a gene editing tool which, in vaccinology, has facilitated the development of recombinant DNA viral-vectored vaccines. Here, we utilize homology-directed repair (HDR) for the generation of a HVT–H7N9 HA bivalent vaccine; a H7N9 HA expression cassette was inserted into the intergenic region between UL45 and UL46 of HVT. To optimize the selection efficiency of our bivalent vaccine, we combined CRISPR/Cas9 with erythrocyte binding to rapidly generate recombinant HVT–H7HA candidate vaccines.
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Shahriari, Amir Ghaffar, and Maziar Habibi-Pirkoohi. "Plant-Based Recombinant Vaccine: Fact or Fiction?" Galen Medical Journal 6, no. 4 (December 29, 2017): 268–80. http://dx.doi.org/10.31661/gmj.v6i4.792.

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In the era of recombinant DNA technology, production of recombinant vaccines in green plants has emerged as an effective approach addressing the problems of traditional vaccine production. Various antigens expressed in different plant species have been so far tested for the production of efficient oral vaccines against human and livestock diseases. However, recombinant vaccines have not yet found a prominent place in pharmaceutical market. There are still many challenges to be addressed to pave the road for commercial production of plant-based recombinant vaccines. Regarding increasing growth in laboratory studies and field trials for development of plant-based vaccines, this review paper provides a comprehensive overview on the topic of plant-derived vaccines and related issues. [GMJ.2017;6(4):268-80] DOI:10.22086/gmj.v6i3.792
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Pastoret, P. P., D. Boulanger, and B. Brochier. "Field trials of a recombinant rabies vaccine." Parasitology 110, S1 (March 1995): S37—S42. http://dx.doi.org/10.1017/s0031182000001475.

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SummaryTo improve both safety and stability of the vaccines used in the field to vaccinate foxes against rabies by the oral route, a recombinant vaccinia virus, expressing the glycoprotein of rabies virus (VVTGgRAB) has been developed. VVTGgRAB innocuity was verified in target species and in domestic animals as well as in numerous wild animal species that could compete with the red fox in consuming vaccine baits in Europe. Oral immunization of foxes, by distributing VVTGgRAB vaccine-baits, was undertaken for the whole infected area in Belgium (10000 km2). Five campaigns of fox vaccination, were carried out from autumn 1989 until 1991. Each time, 150000 vaccine-baits were dropped by air at a mean density of 15 per km2. These campaigns induced a drastic decrease in the incidence of rabies and the elimination of the disease from 80% of the initially infected area. Regarding the geographical evolution of rabies in Belgium and in adjacent regions in neighbouring countries, new spatial strategies for bait dispersal were planned for 1992, 1993 and 1994: successive confined campaigns were carried out along political borders only. These campaigns induced a new decrease of incidence; no rabid fox could be detected in 1993 in spite of an improved epidemiological surveillance. In 1994, rabies was again confirmed in 13 foxes collected in an area close to the French border. These cases demonstrate the persistence of a border rabies focus and justify further restricted vaccination campaigns.
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Berg, Michael G., Robert J. Adams, Ratish Gambhira, Mark C. Siracusa, Alan L. Scott, Richard B. S. Roden, and Gary Ketner. "Immune Responses in Macaques to a Prototype Recombinant Adenovirus Live Oral Human Papillomavirus 16 Vaccine." Clinical and Vaccine Immunology 21, no. 9 (July 2, 2014): 1224–31. http://dx.doi.org/10.1128/cvi.00197-14.

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ABSTRACTImmunization with human papillomavirus (HPV) L1 virus-like particles (VLPs) prevents infection with HPV. However, the expense and logistical demands of current VLP vaccines will limit their widespread use in resource-limited settings, where most HPV-induced cervical cancer occurs. Live oral adenovirus vaccines have properties that are well-suited for use in such settings. We have described a live recombinant adenovirus vaccine prototype that produces abundant HPV16 L1 protein from the adenovirus major late transcriptional unit and directs the assembly of HPV16 VLPs in tissue culture. Recombinant-derived VLPs potently elicit neutralizing antibodies in mice. Here, we characterize the immune response to the recombinant after dual oral and intranasal immunization of pigtail macaques, in which the virus replicates as it would in immunized humans. The immunization of macaques induced vigorous humoral responses to adenovirus capsid and nonstructural proteins, although, surprisingly, not against HPV L1. In contrast, immunization elicited strong T-cell responses to HPV VLPs as well as adenovirus virions. T-cell responses arose immediately after the primary immunization and were boosted by a second immunization with recombinant virus. T-cell immunity contributes to protection against a wide variety of pathogens, including many viruses. The induction of a strong cellular response by the recombinant indicates that live adenovirus recombinants have potential as vaccines for those agents. These studies encourage and will inform the continued development of viable recombinant adenovirus vaccines.
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McAllister, Andrés, Alejandra E. Arbetman, Stefanie Mandl, Claudia Peña-Rossi, and Raul Andino. "Recombinant Yellow Fever Viruses Are Effective Therapeutic Vaccines for Treatment of Murine Experimental Solid Tumors and Pulmonary Metastases." Journal of Virology 74, no. 19 (October 1, 2000): 9197–205. http://dx.doi.org/10.1128/jvi.74.19.9197-9205.2000.

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ABSTRACT We have genetically engineered an attenuated yellow fever (YF) virus to carry and express foreign antigenic sequences and evaluated the potential of this type of recombinant virus to serve as a safe and effective tumor vaccine. Live-attenuated YF vaccine is one of the most effective viral vaccines available today. Important advantages include its ability to induce long-lasting immunity, its safety, its affordability, and its documented efficacy. In this study, recombinant live-attenuated (strain 17D) YF viruses were constructed to express a cytotoxic T-lymphocyte epitope derived from chicken ovalbumin (SIINFEKL). These recombinant viruses replicated comparably to the 17D vaccine strain in cell culture and stably expressed the ovalbumin antigen, and infected cells presented the antigen in the context of major histocompatibility complex class I. Inoculation of mice with recombinant YF virus elicited SIINFEKL-specific CD8+lymphocytes and induced protective immunity against challenge with lethal doses of malignant melanoma cells expressing ovalbumin. Furthermore, active immunotherapy with recombinant YF viruses induced regression of established solid tumors and pulmonary metastases. Thus, recombinant YF viruses are attractive viral vaccine vector candidates for the development of therapeutic anticancer vaccines.
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22

DAČIĆ, M., R. RESANOVIC, Z. RASIC, M. VALCIC, A. MILOVANOVIC, and M. VELHNER. "Efficacy of recombinant VAXXITEK HVT-IBDv vaccine against very virulent Infectious bursal disease virus (vvIBDv) challenge in layer chicks: A pilot study." Journal of the Hellenic Veterinary Medical Society 69, no. 1 (May 2, 2018): 823. http://dx.doi.org/10.12681/jhvms.16434.

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The infectious bursal disease virus (IBDv) is widespread in poultry flocks all around the world. Various biotypes have emerged and because of that, adequate management practices and vaccination of chicks are of paramount importance for the protection against field strains. One day old Lohmann Brown chicks were vaccinated with intermediate vaccines and the recombinant VAXXITEK HVT-IBDv vaccine formulation, and challenged at 48 days of life with the very virulent IBDv (vvIBDv) strain CH/99. The best protection (100%) was achieved with the recombinant vaccine administered by the subcutaneous or intramuscular route at a day old, while intermediate and intermediate plus vaccines protected 80% of birds from clinical symptoms. The highest bursa body ratio (5.33, 3.50 and 4.12) was accomplished in non- vaccinated and non-challenged birds and birds vaccinated with the VAXXITEK HVT-IBDv vaccine. The recombinant VAXXITEK HVT-IBDv vaccine has provided protection for commercial chicks against challenge with the vvIBDv strain in this experiment. Under field conditions, additional vaccination is possibly needed with supplementary application of live attenuated vaccines. However, the recombinant vector vaccines are providing significant aid against clinical signs and immunosupression caused by the vvIBDv.
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23

Pearl, Karlyn K., Ana A. Ortiz, and William Pearl. "Efficacy of Immunization with a Combination of Serum and Recombinant Hepatitis B Vaccines." Infection Control & Hospital Epidemiology 14, no. 8 (August 1993): 476–78. http://dx.doi.org/10.1086/646783.

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AbstractObjective:To evaluate the efficacy of giving a third dose of recombinant hepatitis B vaccine to healthcare workers who already had received two doses of serum-derived vaccine, which is no longer available in the United States.Design:Volunteers who already had received two standard doses of serum-derived vaccine were given a third dose of either serum or recombinant vaccine in a double-blind fashion. Antibodies to hepatitis B surface antigen were measured at the time of the third immunization, three months later, and one year after the third immunization.Setting:U.S. Army Medical Center, El Paso, Texas.Patients:One hundred healthy healthcare workers.Results:Three months after receiving the third immunization, the serum vaccine group had significantly higher titers than the recombinant vaccine group (P= 0.018). One year after receiving the third immunization, those who received the combined regimen had a mean hepatitis B surface antibody titer less than half that of those who received three doses of serum-derived vaccine. However, both regimens resulted in titers that are considered to confer immunity.Conclusions:A regimen that combines serum and recombinant hepatitis B vaccines may not produce as high an antibody level as three doses of the same vaccine. Those who began immunization with serum vaccine and concluded with recombinant vaccine should be monitored for an accelerated drop in serum antibodies.
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24

Cuccui, Jon, Rebecca M. Thomas, Madeleine G. Moule, Riccardo V. D'Elia, Thomas R. Laws, Dominic C. Mills, Diane Williamson, Timothy P. Atkins, Joann L. Prior, and Brendan W. Wren. "Exploitation of bacterial N -linked glycosylation to develop a novel recombinant glycoconjugate vaccine against Francisella tularensis." Open Biology 3, no. 5 (May 2013): 130002. http://dx.doi.org/10.1098/rsob.130002.

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Glycoconjugate-based vaccines have proved to be effective at producing long-lasting protection against numerous pathogens. Here, we describe the application of bacterial protein glycan coupling technology (PGCT) to generate a novel recombinant glycoconjugate vaccine . We demonstrate the conjugation of the Francisella tularensis O-antigen to the Pseudomonas aeruginosa carrier protein exotoxin A using the Campylobacter jejuni PglB oligosaccharyltransferase . The resultant recombinant F. tularensis glycoconjugate vaccine is expressed in Escherichia coli where yields of 3 mg l −1 of culture were routinely produced in a single-step purification process. Vaccination of BALB/c mice with the purified glycoconjugate boosted IgG levels and significantly increased the time to death upon subsequent challenge with F. tularensis subsp. holarctica . PGCT allows different polysaccharide and protein combinations to be produced recombinantly and could be easily applicable for the production of diverse glycoconjugate vaccines.
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Willadsen, P., P. Bird, G. S. Cobon, and J. Hungerford. "Commercialisation of a recombinant vaccine againstBoophilus microplus." Parasitology 110, S1 (March 1995): S43—S50. http://dx.doi.org/10.1017/s0031182000001487.

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SummaryIncreasingly, there is need for methods to control cattle tick (Boophilus microplus) infestations by the use of non-chemical technology. This need is brought about by a mixture of market forces and the failure or inadequacy of existing technology. A recombinant vaccine has now been developed against the tick. This vaccine relies on the uptake with the blood meal of antibody directed against a critical protein in the tick gut. The isolation of the vaccine antigen, Bm86, and its production as a recombinant protein is briefly described. The vaccine has been tested in the field, has been taken through the full registration process and is now in commercial use in Australia. A related development has occurred in Cuba. The potential for improvement of the current vaccine and for the development of similar vaccines against other haematophagous parasites is discussed.
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Sarmadi, Mahdieh, Azam Gheibi, Hossein Khanahmad, Mohammad Reza Khorramizadeh, Seyed Hossein Hejazi, Noushin Zahedi, Hamidreza Mianesaz, and Khosrow Kashfi. "Design and Characterization of a Recombinant Brucella abortus RB51 Vaccine That Elicits Enhanced T Cell-Mediated Immune Response." Vaccines 10, no. 3 (March 3, 2022): 388. http://dx.doi.org/10.3390/vaccines10030388.

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Brucella abortus vaccines help control bovine brucellosis. The RB51 strain is a live attenuated vaccine with low side effects compared with other live attenuated brucellosis vaccines, but it provides insufficient protective efficacy. Cell-mediated immune responses are critical in resistance against intracellular bacterial infections. Therefore, we hypothesized that the listeriolysin O (LLO) expression of Listeria monocytogenes, BAX, and SMAC apoptotic proteins in strain RB51 could enhance vaccine efficacy and safety. B. abortus RB51 was transformed separately with two broad-host-range plasmids (pbbr1ori-LLO and pBlu–mLLO-BAX-SMAC) constructed from our recent work. pbbr1ori-LLO contains LLO, and pBlu–mLLO-BAX-SMAC contains the mutant LLO and BAX-SMAC fusion gene. The murine macrophage-like cell line J774A.1 was infected with the RB51 recombinant strain containing pBlu-mLLO-BAX-SMAC, RB51 recombinant strain containing LLO, and RB51 strain. The bacterial cytotoxicity and survival and apoptosis of host cells contaminated with our two strain types—RB51 recombinants or the parental RB51—were assessed. Strain RB51 expressing mLLO and BAX-SMAC was tested in BALB/c mice and a cell line for enhanced modulation of IFN-γ production. LDH analysis showed that the RB51-mLLO-BAX-SMAC and RB51-LLO strains expressed higher cytotoxicity in J774A.1 cells than RB51. In addition, RB51 recombinants had lower macrophage survival rates and caused higher levels of apoptosis and necrosis. Mice vaccinated with the RB51 recombinant containing mLLO-BAX-SMAC showed an enhanced Th1 immune response. This enhanced immune response is primarily due to bacterial endosome escape and bacterial antigens, leading to improved apoptosis and cross-priming. This potentially enhanced TCD8+- and T cell-mediated immunity leads to the increased safety and potency of the RB51 recombinant (RB51 mLLO-BAX-SMAC) as a vaccine candidate against B. abortus.
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Tang, Na, Yaoyao Zhang, Yashar Sadigh, Katy Moffat, Zhiqiang Shen, Venugopal Nair, and Yongxiu Yao. "Generation of A Triple Insert Live Avian Herpesvirus Vectored Vaccine Using CRISPR/Cas9-Based Gene Editing." Vaccines 8, no. 1 (February 21, 2020): 97. http://dx.doi.org/10.3390/vaccines8010097.

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Herpesvirus of turkeys (HVT), used originally as a vaccine against Marek’s disease (MD), has recently been shown to be a highly effective viral vector for generation of recombinant vaccines that deliver protective antigens of other avian pathogens. Until the recent launch of commercial HVT-vectored dual insert vaccines, most of the HVT-vectored vaccines in the market carry a single foreign gene and are usually developed with slow and less efficient conventional recombination methods. There is immense value in developing multivalent HVT-vectored vaccines capable of inducing simultaneous protection against multiple avian pathogens, particularly to overcome the interference between individual recombinant HVT vaccines. Here we demonstrate the use of a previously developed CRISPR/Cas9 gene editing protocol for the insertion of ILTV gD-gI and the H9N2 AIV hemagglutinin expression cassettes into the distinct locations of the recombinant HVT-IBDV VP2 viral genome, to generate the triple insert HVT-VP2-gDgI-HA recombinant vaccine. The insertion, protein expression, and stability of each insert were then evaluated by PCR, immunostaining and Western blot analyses. The successful generation of the first triple insert recombinant HVT vaccine with the potential for the simultaneous protection against three major avian viral diseases in addition to MD is a major innovation in vaccination-based control of major poultry diseases.
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Tarcha, Eric J., Venkatesha Basrur, Chiung-Yu Hung, Malcolm J. Gardner, and Garry T. Cole. "Multivalent Recombinant Protein Vaccine against Coccidioidomycosis." Infection and Immunity 74, no. 10 (October 2006): 5802–13. http://dx.doi.org/10.1128/iai.00961-06.

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ABSTRACT Coccidioidomycosis is a human respiratory disease that is endemic to the southwestern United States and is caused by inhalation of the spores of a desert soilborne fungus. Efforts to develop a vaccine against this disease have focused on identification of T-cell-reactive antigens derived from the parasitic cell wall which can stimulate protective immunity against Coccidioides posadasii infection in mice. We previously described a productive immunoproteomic/bioinformatic approach to the discovery of vaccine candidates which makes use of the translated genome of C. posadasii and a computer-based method of scanning deduced sequences of seroreactive proteins for epitopes that are predicted to bind to human major histocompatibility (MHC) class II-restricted molecules. In this study we identified a set of putative cell wall proteins predicted to contain multiple, promiscuous MHC II binding epitopes. Three of these were expressed by Escherichia coli, combined in a vaccine, and tested for protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived beyond 90 days after intranasal challenge, and the majority cleared the pathogen. We suggest that the multicomponent vaccine stimulates a broader range of T-cell clones than the single recombinant protein vaccines and thereby may be capable of inducing protection in an immunologically heterogeneous human population.
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Barouch, Dan H., Paul F. McKay, Shawn M. Sumida, Sampa Santra, Shawn S. Jackson, Darci A. Gorgone, Michelle A. Lifton, et al. "Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines." Journal of Virology 77, no. 16 (August 15, 2003): 8729–35. http://dx.doi.org/10.1128/jvi.77.16.8729-8735.2003.

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ABSTRACT Heterologous “prime-boost” regimens that involve priming with plasmid DNA vaccines and boosting with recombinant viral vectors have been shown to elicit potent virus-specific cytotoxic T-lymphocyte responses. Increasing evidence, however, suggests that the utility of recombinant viral vectors in human populations will be significantly limited by preexisting antivector immunity. Here we demonstrate that the coadministration of plasmid chemokines and colony-stimulating factors with plasmid DNA vaccines markedly increases the immunogenicity of DNA prime-recombinant adenovirus serotype 5 (rAd5) boost and DNA prime-recombinant vaccinia virus (rVac) boost vaccine regimens in BALB/c mice. In mice with preexisting anti-Ad5 immunity, priming with the DNA vaccine alone followed by rAd5 boosting elicited only marginal immune responses. In contrast, cytokine-augmented DNA vaccine priming followed by rAd5 vector boosting was able to generate potent immune responses in mice with preexisting anti-Ad5 immunity. These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity.
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Kumar, Pawan, Tamer A. Sharafeldin, Rahul Kumar, Qinfeng Huang, Yuying Liang, Sagar M. Goyal, Robert E. Porter, Hinh Ly, and Sunil K. Mor. "Development of a Recombinant Pichinde Virus-Vectored Vaccine against Turkey Arthritis Reovirus and Its Immunological Response Characterization in Vaccinated Animals." Pathogens 10, no. 2 (February 13, 2021): 197. http://dx.doi.org/10.3390/pathogens10020197.

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Vaccination may be an effective way to reduce turkey arthritis reovirus (TARV)-induced lameness in turkey flocks. However, there are currently no commercial vaccines available against TARV infection. Here, we describe the use of reverse genetics technology to generate a recombinant Pichinde virus (PICV) that expresses the Sigma C and/or Sigma B proteins of TARV as antigens. Nine recombinant PICV-based TARV vaccines were developed carrying the wild-type S1 (Sigma C) and/or S3 (Sigma B) genes from three different TARV strains. In addition, three recombinant PICV-based TARV vaccines were produced carrying codon-optimized S1 and/or S3 genes of a TARV strain. The S1 and S3 genes and antigens were found to be expressed in virus-infected cells via reverse transcriptase polymerase chain reaction (RT-PCR) and the direct fluorescent antibody (DFA) technique, respectively. Turkey poults inoculated with the recombinant PICV-based TARV vaccine expressing the bivalent TARV S1 and S3 antigens developed high anti-TARV antibody titers, indicating the immunogenicity (and safety) of this vaccine. Future in vivo challenge studies using a turkey reovirus infection model will determine the optimum dose and protective efficacy of this recombinant virus-vectored candidate vaccine.
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Krasilnikov, I. V., T. I. Vinogradova, M. Djonovic, N. V. Zabolotnykh, S. A. Arakelov, M. Z. Dogonadze, and V. G. Lunin. "TB skin test recombinant proteins as vaccine candidates." Genes & Cells 17, no. 2 (September 25, 2022): 47–55. http://dx.doi.org/10.23868/202209007.

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Incomplete protection of BCG vaccines, high variability of tuberculosis strains, together with the growing antibiotic resistance of mycobacterium tuberculosis, actualize the need to develop new anti-tuberculosis vaccines. Several novel experimental candidate vaccines based on recombinant proteins, such as those based on the M. tuberculosis ESAT-6 and CFP-10 antigens, are currently being studied in clinical trials. The genome region coding for ESAT-6 and CFP-10 antigens is deleted in BCG strains, so the BCG-immunized individuals cannot develop an immune response against the recombinant ESAT-6/CFP-10 antigen. Therefore, a positive immune reaction to these antigens in TB tests indicates the tested individual has earlier been exposed to M. tuberculosis. The ESAT-6/CFP-10 fusion recombinant antigen was, thus, selected as an immunogen to be evaluated on its potential to induce protective immunity against tuberculosis in a mice model when combined with a birch bark betulin-based vaccine adjuvant. The effect of use was assessed based on the results of histological evaluation of the infected lung tissue in mice and the Mtb lung content. The results herein reported eventually demonstrated that the use of corpuscular adjuvant-based (betulin) ESAT-6/CFP-10 vaccine preparation can induce the immune response commensurate to that of when immunized with the BCG vaccine.
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Rizqoh, Debie. "Genetic Engineering Technique in Virus-Like Particle Vaccine Construction." Jurnal Kesehatan Masyarakat Indonesia 16, no. 4 (December 31, 2021): 203. http://dx.doi.org/10.26714/jkmi.16.4.2021.203-211.

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Vaccine becomes a very effective strategy to deal with various infectious diseases even to the point of eradication as in the smalpox virus. At present many conventional vaccines such as inactivated and live-attenuated vaccines. However, these vaccine methods have side effects on the population. Viral-like particle (VLP) is an alternative vaccine based on recombinant DNA technology that is safe with the same immunogenicity as conventional viruses. This vaccine has been shown to induce humoral immune responses mediated by antibodies and cellular immune responses mediated by cytotoxic T cells. With these advantages, currently various types of vaccines have only been developed on a VLP basis. VLP can be produced from a variety of recombinant gene expression systems including bacterial cell expression systems, yeast cells, insect cells, mammalian cells, plant cells, and cell-free systems.
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Noyce, Ryan S., Landon W. Westfall, Siobhan Fogarty, Karen Gilbert, Onesmo Mpanju, Helen Stillwell, José Esparza, et al. "Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox Challenge." Viruses 15, no. 2 (January 26, 2023): 356. http://dx.doi.org/10.3390/v15020356.

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The ongoing global Monkeypox outbreak that started in the spring of 2022 has reinforced the importance of protecting the population using live virus vaccines based on the vaccinia virus (VACV). Smallpox also remains a biothreat and although some U.S. military personnel are immunized with VACV, safety concerns limit its use in other vulnerable groups. Consequently, there is a need for an effective and safer, single dose, live replicating vaccine against both viruses. One potential approach is to use the horsepox virus (HPXV) as a vaccine. Contemporary VACV shares a common ancestor with HPXV, which from the time of Edward Jenner and through the 19th century, was extensively used to vaccinate against smallpox. However, it is unknown if early HPXV-based vaccines exhibited different safety and efficacy profiles compared to modern VACV. A deeper understanding of HPXV as a vaccine platform may allow the construction of safer and more effective vaccines against the poxvirus family. In a proof-of-concept study, we vaccinated cynomolgus macaques with TNX-801, a recombinant chimeric horsepox virus (rcHPXV), and showed that the vaccine elicited protective immune responses against a lethal challenge with monkeypox virus (MPXV), strain Zaire. The vaccine was well tolerated and protected animals from the development of lesions and severe disease. These encouraging data support the further development of TNX-801.
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Ourmanov, Ilnour, Charles R. Brown, Bernard Moss, Miles Carroll, Linda Wyatt, Liuobov Pletneva, Simoy Goldstein, David Venzon, and Vanessa M. Hirsch. "Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV." Journal of Virology 74, no. 6 (March 15, 2000): 2740–51. http://dx.doi.org/10.1128/jvi.74.6.2740-2751.2000.

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ABSTRACT Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741–3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.
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35

Tseng, Ta-Yuan, Yee-Chen Liu, Yu-Chen Hsu, Poa-Chun Chang, Ming-Kun Hsieh, Jui-Hung Shien, and Shan-Chia Ou. "Preparation of Chicken Anemia Virus (CAV) Virus-Like Particles and Chicken Interleukin-12 for Vaccine Development Using a Baculovirus Expression System." Pathogens 8, no. 4 (November 23, 2019): 262. http://dx.doi.org/10.3390/pathogens8040262.

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Chicken infectious anemia (CIA) is a poultry disease that causes huge economic losses in the poultry industry worldwide. Commercially available CIA vaccines are derived from wild-type chicken anemia viruses (CAVs) by serial passage in cells or chicken embryos. However, these vaccinal viruses are not completely attenuated; therefore, they can be transmitted vertically and horizontally, and may induce clinical symptoms in young birds. In this study, we sought to eliminate these issues by developing a subunit vaccine exploiting the CAV structural proteins, engineering recombinant baculovirus-infected Spodoptera frugiperda (Sf9) cells that contained both the viral protein 1 (VP1) and VP2 of CAV. Moreover, we produced single-chain chicken interleukin-12 (chIL-12) in the same system, to serve as an adjuvant. The recombinant VP1 was recognized by chicken anti-CAV polyclonal antibodies in Western blotting and immunofluorescence assays, and the bioactivity of the recombinant chIL-12 was confirmed by stimulating interferon-γ (IFN-γ) secretion in chicken splenocytes. Furthermore, the ability of the recombinant VP1 to generate self-assembling virus-like particles (VLPs) was confirmed by transmission electron microscopy. Specific pathogen-free (SPF) chickens inoculated with VLPs and co-administered the recombinant chIL-12 induced high CAV-specific antibodies and cell-mediated immunity. Taken together, the VLPs produced by the baculovirus expression system have the potential to be a safe and effective CIA vaccine. Finally, we demonstrated the utility of recombinant chIL-12 as an adjuvant for poultry vaccine development.
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36

Kim, Joseph W., Jennifer L. Marte, Nishith K. Singh, Christopher Ryan Heery, Ravi Amrit Madan, Mary Pazdur, Sheri McMahon, et al. "Safety profile of recombinant poxviral TRICOM vaccines." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16036-e16036. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16036.

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e16036 Background: Recombinant (rec) poxviruses have been developed as therapeutic cancer vaccines. A multi-institutional, randomized phase II trial of poxviral vaccine, PROSTVAC-V/F, suggested an improvement in median overall survival in men with metastatic castration resistant prostate cancer. A phase III trial in this same population is accruing. Accumulating data suggest a favorable safety profile of the poxviral vaccines (vacs). Methods: We reviewed all vaccine injections (inj) from 297 patients (pts) in 9 clinical trials involving poxviral vaccines. Vacs consisted of rec vaccinia and rec fowlpox encoded with 3 human costimulatory molecules (TRICOM), and a) prostate specific antigen, or b) carcinoembryonic antigen +/-mucin-1. Vacs were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all pts. 21 pts were also vaccinated intra-tumorally. 84 pts received concurrent treatments, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide in 4 of these trials. All 9 trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF), or rec fowlpox encoding GM-CSF as an immune adjuvant. We report the grade >=2 adverse events (AEs) at least possibly attributed to vaccine. Results: A total of 1,793 poxviral inj were given. 33% (593) of all inj were associated with grade >=2 vaccination emergent AEs. Of those, 25.3 % (454) were local inj site reactions; none serious. There was no contact transmission or inadvertent inoculation. One patient experienced grade 4 myocardial infarction and thrombotic thrombocytopenic purpura (TTP) reported as possibly related to vaccine. Below is the summary of AEs. Conclusions: Recombinant poxviral TRICOM vaccines appear safe and well tolerated at a broad range of doses, routes of administration and in combination with other treatments. Clinical trial information: NCT00081848, NCT00088413, NCT00060528, NCT00060528, NCT00078585, NCT00096551, NCT00113984. [Table: see text]
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37

&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 1378 (November 2011): 19. http://dx.doi.org/10.2165/00128415-201113780-00067.

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38

&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 702 (May 1998): 7. http://dx.doi.org/10.2165/00128415-199807020-00016.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 708 (July 1998): 7. http://dx.doi.org/10.2165/00128415-199807080-00022.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 710 (July 1998): 8. http://dx.doi.org/10.2165/00128415-199807100-00025.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 714 (August 1998): 9. http://dx.doi.org/10.2165/00128415-199807140-00029.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 720 (September 1998): 8. http://dx.doi.org/10.2165/00128415-199807200-00018.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 722 (October 1998): 9. http://dx.doi.org/10.2165/00128415-199807220-00024.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 724 (October 1998): 8. http://dx.doi.org/10.2165/00128415-199807240-00024.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 727 (November 1998): 8. http://dx.doi.org/10.2165/00128415-199807270-00021.

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46

&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 739 (February 1999): 9. http://dx.doi.org/10.2165/00128415-199907390-00028.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 741 (March 1999): 10. http://dx.doi.org/10.2165/00128415-199907410-00030.

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48

&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 747 (April 1999): 7. http://dx.doi.org/10.2165/00128415-199907470-00019.

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49

&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 1194-1195 (March 2008): 20. http://dx.doi.org/10.2165/00128415-200811940-00069.

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&NA;. "Hepatitis B vaccine recombinant." Reactions Weekly &NA;, no. 1139 (February 2007): 14. http://dx.doi.org/10.2165/00128415-200711390-00048.

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