Journal articles: 'Nanoparticle-based vaccines'

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Heuts, Jeroen, Wim Jiskoot, Ferry Ossendorp, and Koen van der Maaden. "Cationic Nanoparticle-Based Cancer Vaccines." Pharmaceutics 13, no. 5 (April 21, 2021): 596. http://dx.doi.org/10.3390/pharmaceutics13050596.

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Cationic nanoparticles have been shown to be surprisingly effective as cancer vaccine vehicles in preclinical and clinical studies. Cationic nanoparticles deliver tumor-associated antigens to dendritic cells and induce immune activation, resulting in strong antigen-specific cellular immune responses, as shown for a wide variety of vaccine candidates. In this review, we discuss the relation between the cationic nature of nanoparticles and the efficacy of cancer immunotherapy. Multiple types of lipid- and polymer-based cationic nanoparticulate cancer vaccines with various antigen types (e.g., mRNA, DNA, peptides and proteins) and adjuvants are described. Furthermore, we focus on the types of cationic nanoparticles used for T-cell induction, especially in the context of therapeutic cancer vaccination. We discuss different cationic nanoparticulate vaccines, molecular mechanisms of adjuvanticity and biodistribution profiles upon administration via different routes. Finally, we discuss the perspectives of cationic nanoparticulate vaccines for improving immunotherapy of cancer.

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Stephens, Laura M., and Steven M. Varga. "Nanoparticle vaccines against respiratory syncytial virus." Future Virology 15, no. 11 (November 2020): 763–78. http://dx.doi.org/10.2217/fvl-2020-0174.

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Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in infants, the elderly and immunocompromised individuals. Despite the global burden, there is no licensed vaccine for RSV. Recent advances in the use of nanoparticle technology have provided new opportunities to address some of the limitations of conventional vaccines. Precise control over particle size and surface properties enhance antigen stability and prolong antigen release. Particle size can also be modified to target specific antigen-presenting cells in order to induce specific types of effector T-cell responses. Numerous nanoparticle-based vaccines are currently being evaluated for RSV including inorganic, polymeric and virus-like particle-based formulations. Here, we review the potential advantages of using different nanoparticle formulations in a vaccine for RSV, and discuss many examples of safe, and effective vaccines currently in both preclinical and clinical stages of testing.

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Marasini, Nirmal, Mariusz Skwarczynski, and Istvan Toth. "Intranasal delivery of nanoparticle-based vaccines." Therapeutic Delivery 8, no. 3 (March 2017): 151–67. http://dx.doi.org/10.4155/tde-2016-0068.

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Marasini, Nirmal, Mariusz Skwarczynski, and Istvan Toth. "Oral delivery of nanoparticle-based vaccines." Expert Review of Vaccines 13, no. 11 (August 26, 2014): 1361–76. http://dx.doi.org/10.1586/14760584.2014.936852.

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Bezbaruah, Rajashri, Vivek P. Chavda, Lawandashisha Nongrang, Shahnaz Alom, Kangkan Deka, Tutumoni Kalita, Farak Ali, Bedanta Bhattacharjee, and Lalitkumar Vora. "Nanoparticle-Based Delivery Systems for Vaccines." Vaccines 10, no. 11 (November 17, 2022): 1946. http://dx.doi.org/10.3390/vaccines10111946.

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Vaccination is still the most cost-effective way to combat infectious illnesses. Conventional vaccinations may have low immunogenicity and, in most situations, only provide partial protection. A new class of nanoparticle-based vaccinations has shown considerable promise in addressing the majority of the shortcomings of traditional and subunit vaccines. This is due to recent breakthroughs in chemical and biological engineering, which allow for the exact regulation of nanoparticle size, shape, functionality, and surface characteristics, resulting in improved antigen presentation and robust immunogenicity. A blend of physicochemical, immunological, and toxicological experiments can be used to accurately characterize nanovaccines. This narrative review will provide an overview of the current scenario of the nanovaccine.

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Du, Lanying, Yang Yang, Xiujuan Zhang, and Fang Li. "Recent advances in nanotechnology-based COVID-19 vaccines and therapeutic antibodies." Nanoscale 14, no. 4 (2022): 1054–74. http://dx.doi.org/10.1039/d1nr03831a.

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This review summarizes the nanotechnology-based COVID-19 vaccines and therapeutics, including protein nanoparticle-based vaccines, lipid nanoparticle-formulated mRNA vaccines, and nanobodies as unique therapeutic antibodies.

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Bernasconi, Valentina, Karin Norling, Marta Bally, Fredrik Höök, and Nils Y. Lycke. "Mucosal Vaccine Development Based on Liposome Technology." Journal of Immunology Research 2016 (2016): 1–16. http://dx.doi.org/10.1155/2016/5482087.

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Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines.

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Zhang, Naru, Qianting Ji, Zezhong Liu, Kaiming Tang, Yubin Xie, Kangchen Li, Jie Zhou, et al. "Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant." Viruses 14, no. 3 (February 28, 2022): 501. http://dx.doi.org/10.3390/v14030501.

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The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.

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Sung, Hyo-Dong, Nayeon Kim, Yeram Lee, and Eun Jung Lee. "Protein-Based Nanoparticle Vaccines for SARS-CoV-2." International Journal of Molecular Sciences 22, no. 24 (December 14, 2021): 13445. http://dx.doi.org/10.3390/ijms222413445.

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The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has upended healthcare systems and economies around the world. Rapid understanding of the structural biology and pathogenesis of SARS-CoV-2 has allowed the development of emergency use or FDA-approved vaccines and various candidate vaccines. Among the recently developed SARS-CoV-2 candidate vaccines, natural protein-based nanoparticles well suited for multivalent antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses are currently being investigated. This mini-review presents recent innovations in protein-based nanoparticle vaccines against SARS-CoV-2. The design and strategy of displaying antigenic domains, including spike protein, receptor-binding domain (RBD), and other domains on the surface of various protein-based nanoparticles and the performance of the developed nanoparticle-based vaccines are highlighted. In the final part of this review, we summarize and discuss recent advances in clinical trials and provide an outlook on protein-based nanoparticle vaccines.

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Hu, Yun, Daniel Smith, Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, and Chenming Zhang. "Alum as an adjuvant for nanoparticle based vaccines: A case study with a hybrid nanoparticle-based nicotine vaccine." Nanomedicine: Nanotechnology, Biology and Medicine 20 (August 2019): 102023. http://dx.doi.org/10.1016/j.nano.2019.102023.

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Poudel, Uddab, Saurav Pantha, and Krishna Kaphle. "The status of development of nanoparticle-based swine influenza vaccines: A review." Journal of Biomedical Sciences 6, no. 1 (October 27, 2019): 6–11. http://dx.doi.org/10.3126/jbs.v6i1.26161.

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Background Swine are the most important meat animal, famous for white meat, which are prepared as ham, bacon, gammon, sausages and pork. Swine are valuable animals and they are physiologically, immunologically and anatomically similar to humans and their organ can be transplanted to the humans. Due to modernization, the cultural food restriction has lost in the people of urban communities and among the younger generations in Nepal. Gradually changing feeding habit of Nepalese has proven pork to be a useful addition to the food menu. Not only 8.7 lakhs swine in Nepal but the global pig population which occupy 769.05 million are suffering every day from new challenges and threats from very harmful pathogens and diseases like swine dysentery, coccidiosis, swine influenza, etc. Swine influenza is highly contagious rapidly spreading zoonotic viral disease of pigs characterized by febrile respiratory disease often complicated with secondary bacterial infections. Vaccines are only tool for prophylactic measures. There is big challenge for vaccine researchers, manufacturers and scientists for development of effective vaccine regarding swine influenza. Currently available flu vaccines are capable of homologous protection of virus but fail to induce cross protection against frequently evolving heterologous viruses. In this review, we discuss the status of novel nanoparticle-based approach of swine influenza virus vaccine development contributed significantly by Nepalese scientist and the future directions to control this economically important swine disease.

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Wieczorek, Klaudia, Barbara Szutkowska, and Elzbieta Kierzek. "Anti-Influenza Strategies Based on Nanoparticle Applications." Pathogens 9, no. 12 (December 3, 2020): 1020. http://dx.doi.org/10.3390/pathogens9121020.

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Influenza virus has the potential for being one of the deadliest viruses, as we know from the pandemic’s history. The influenza virus, with a constantly mutating genome, is becoming resistant to existing antiviral drugs and vaccines. For that reason, there is an urgent need for developing new therapeutics and therapies. Despite the fact that a new generation of universal vaccines or anti-influenza drugs are being developed, the perfect remedy has still not been found. In this review, various strategies for using nanoparticles (NPs) to defeat influenza virus infections are presented. Several categories of NP applications are highlighted: NPs as immuno-inducing vaccines, NPs used in gene silencing approaches, bare NPs influencing influenza virus life cycle and the use of NPs for drug delivery. This rapidly growing field of anti-influenza methods based on nanotechnology is very promising. Although profound research must be conducted to fully understand and control the potential side effects of the new generation of antivirals, the presented and discussed studies show that nanotechnology methods can effectively induce the immune responses or inhibit influenza virus activity both in vitro and in vivo. Moreover, with its variety of modification possibilities, nanotechnology has great potential for applications and may be helpful not only in anti-influenza but also in the general antiviral approaches.

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Lebel, Marie-Ève, Karine Chartrand, Denis Leclerc, and Alain Lamarre. "Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants." Vaccines 3, no. 3 (August 5, 2015): 620–37. http://dx.doi.org/10.3390/vaccines3030620.

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Pulliam, Brian, Jean C. Sung, and David A. Edwards. "Design of nanoparticle-based dry powder pulmonary vaccines." Expert Opinion on Drug Delivery 4, no. 6 (October 31, 2007): 651–63. http://dx.doi.org/10.1517/17425247.4.6.651.

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Guerrini, Giuditta, Sabrina Gioria, Aisha V. Sauer, Simone Lucchesi, Francesca Montagnani, Gabiria Pastore, Annalisa Ciabattini, Donata Medaglini, and Luigi Calzolai. "Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration." International Journal of Molecular Sciences 23, no. 16 (August 9, 2022): 8838. http://dx.doi.org/10.3390/ijms23168838.

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PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.

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Chandrasekar, Shaswath S., Yashdeep Phanse, Mariah Riel, Rachel E. Hildebrand, Mostafa Hanafy, Jorge E. Osorio, Sherein S. Abdelgayed, and Adel M. Talaat. "Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2." Viruses 14, no. 6 (June 10, 2022): 1262. http://dx.doi.org/10.3390/v14061262.

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Antibody measurements are primarily used to evaluate experimental and approved COVID-19 vaccines, which is unilateral considering our immune responses’ complex nature. Previously, we showed that nanoparticle plasmid DNA adjuvant system, QAC, and MVA based vaccines were immunogenic against SARS-CoV-2. Here, we report on the protective efficacy of systemic humoral and mucosal cell-mediated immune responses in transgenic mice models against SARS-CoV-2 following nanoparticle immunization. Parenteral, intramuscular administration of QAC-based plasmid DNA vaccine-encoding SARS-CoV-2 S and N led to the induction of significant serum neutralizing humoral responses, which reduced viral burden in the lungs and prevented viral dissemination to the brain. In contrast, the mucosal, intranasal administration of a heterologous vaccine elicited significant mucosal cell-mediated immune responses in the lungs that limited lung viral replication. The presented results demonstrate that serum neutralizing humoral and local lung T-cell immune responses are critical for the control of SARS-CoV-2 replication.

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Cappelli, Luigia, Paolo Cinelli, Fabiola Giusti, Ilaria Ferlenghi, Sabrina Utrio-Lanfaloni, Newton Wahome, Matthew James Bottomley, Domenico Maione, and Roberta Cozzi. "Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion." PLOS ONE 17, no. 9 (September 16, 2022): e0273322. http://dx.doi.org/10.1371/journal.pone.0273322.

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Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal β-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including virus-like particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in Escherichia coli and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the β-barrel from fHbp, including ferritin, a de novo designed aldolase from Thermotoga maritima, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structure-based design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens.

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Semple, Sean C., Robert Leone, Christopher J. Barbosa, Ying K. Tam, and Paulo J. C. Lin. "Lipid Nanoparticle Delivery Systems to Enable mRNA-Based Therapeutics." Pharmaceutics 14, no. 2 (February 11, 2022): 398. http://dx.doi.org/10.3390/pharmaceutics14020398.

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The world raced to develop vaccines to protect against the rapid spread of SARS-CoV-2 infection upon the recognition of COVID-19 as a global pandemic. A broad spectrum of candidates was evaluated, with mRNA-based vaccines emerging as leaders due to how quickly they were available for emergency use while providing a high level of efficacy. As a modular technology, the mRNA-based vaccines benefitted from decades of advancements in both mRNA and delivery technology prior to the current global pandemic. The fundamental lessons of the utility of mRNA as a therapeutic were pioneered by Dr. Katalin Kariko and her colleagues, perhaps most notably in collaboration with Drew Weissman at University of Pennsylvania, and this foundational work paved the way for the development of the first ever mRNA-based therapeutic authorized for human use, COMIRNATY®. In this Special Issue of Pharmaceutics, we will be honoring Dr. Kariko for her great contributions to the mRNA technology to treat diseases with unmet needs. In this review article, we will focus on the delivery platform, the lipid nanoparticle (LNP) carrier, which allowed the potential of mRNA therapeutics to be realized. Similar to the mRNA technology, the development of LNP systems has been ongoing for decades before culminating in the success of the first clinically approved siRNA-LNP product, ONPATTRO®, a treatment for an otherwise fatal genetic disease called transthyretin amyloidosis. Lessons learned from the siRNA-LNP experience enabled the translation into the mRNA platform with the eventual authorization and approval of the mRNA-LNP vaccines against COVID-19. This marks the beginning of mRNA-LNP as a pharmaceutical option to treat genetic diseases.

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Chen, Long, Hao Qin, Ruifang Zhao, Xiao Zhao, Liangru Lin, Yang Chen, Yixuan Lin, et al. "Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines." Science Translational Medicine 13, no. 601 (July 7, 2021): eabc2816. http://dx.doi.org/10.1126/scitranslmed.abc2816.

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Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on Escherichia coli cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8+ T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.

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Khan, Masood Alam, and Arif Khan. "Role of NKT Cells during Viral Infection and the Development of NKT Cell-Based Nanovaccines." Vaccines 9, no. 9 (August 26, 2021): 949. http://dx.doi.org/10.3390/vaccines9090949.

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Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and the strategies of viruses to evade the functioning of NKT cell have been illustrated. The nanoparticle-based formulations have superior immunoadjuvant potential by facilitating the efficient antigen processing and presentation that favorably elicits the antigen-specific immune response. Finally, the immunoadjuvant potential of the NKT cell ligand was explored in the development of antiviral vaccines. The use of an NKT cell-activating nanoparticle-based vaccine delivery system was supported in order to avoid the NKT cell anergy. The results from the animal and preclinical studies demonstrated that nanoparticle-incorporated NKT cell ligands may have potential implications as an immunoadjuvant in the formulation of an effective antiviral vaccine that is capable of eliciting the antigen-specific activation of the cell-mediated and humoral immune responses.

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Chen, Pu-Guang, Zhi-Hua Huang, Zhan-Yi Sun, Yue Gao, Yan-Fang Liu, Lei Shi, Yong-Xiang Chen, Yu-Fen Zhao, and Yan-Mei Li. "Chitosan nanoparticles based nanovaccines for cancer immunotherapy." Pure and Applied Chemistry 89, no. 7 (July 26, 2017): 931–39. http://dx.doi.org/10.1515/pac-2016-0913.

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AbstractCancer immunotherapy based on tumor vaccine is very promising and intriguing for carcinoma treatment. Herein, antitumor nanovaccines consisting of self-assembled chitosan (CS) nanoparticles and two-component mucin1 (MUC1) glycopeptide antigens were reported. Two different kinds of polyanionic electrolyte [sodium tripolyphosphate (TPP) and γ-poly-L-glutamic acid (γ-PGA)] were combined with chitosan polymers to fabricate the diameter of nearly 400–500 nm CS nanoparticles by electrostatic interactions. The nanovaccines were constructed by physically mixing MUC1 glycopeptide antigens with CS nanoparticles, which reduced vaccine constructing complexity compared with traditional chemical total synthetic vaccines. Immunological studies revealed that the CS/γ-PGA nanoparticle could dramatically enhance the immunogenicity of peptide epitope and produce significantly high titers of IgG antibody which was even better than Freund’s adjuvant-containing vaccines.

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Liu, Ting, Yang Tian, Aiping Zheng, and Chunying Cui. "Design Strategies for and Stability of mRNA–Lipid Nanoparticle COVID-19 Vaccines." Polymers 14, no. 19 (October 6, 2022): 4195. http://dx.doi.org/10.3390/polym14194195.

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Messenger RNA (mRNA) vaccines have shown great preventive potential in response to the novel coronavirus (COVID-19) pandemic. The lipid nanoparticle (LNP), as a non-viral vector with good safety and potency factors, is applied to mRNA delivery in the clinic. Among the recently FDA-approved SARS-CoV-2 mRNA vaccines, lipid-based nanoparticles have been shown to be well-suited to antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses. However, a design strategy for optimal mRNA-LNP vaccines has not been fully elaborated. In this review, we comprehensively and systematically discuss the research strategies for mRNA-LNP vaccines against COVID-19, including antigen and lipid carrier selection, vaccine preparation, quality control, and stability. Meanwhile, we also discuss the potential development directions for mRNA–LNP vaccines in the future. We also conduct an in-depth review of those technologies and scientific insights in regard to the mRNA-LNP field.

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Zhao, Zongmin, Yun Hu, Theresa Harmon, Paul Pentel, Marion Ehrich, and Chenming Zhang. "Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine." Molecular Pharmaceutics 16, no. 6 (May 10, 2019): 2766–75. http://dx.doi.org/10.1021/acs.molpharmaceut.9b00279.

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Gourapura, Renukaradhya J., Ninoshkaly Feliciano-Ruiza, Sankar Renu, Fangjia Lu, Yi Han, Jennifer Schrock, Santosh Dhakal, Veerupaxagouda Patil, and Harm HogenEsch. "Corn based nanoparticle delivered inactivated influenza virus vaccine intranasally augments mucosal immune response in pigs." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 166.4. http://dx.doi.org/10.4049/jimmunol.204.supp.166.4.

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Abstract Swine influenza A virus (SwIV) causes respiratory tract infection in pigs. Available SwIV vaccines fail to provide cross-protective immunity in pigs. Nano-11 is an amphiphilic nanoparticle (70–80nm) obtained from sweet corn-derived phytoglycogen. Nano-11 carries high surface positive charge and thus facilitates easy preparation of nanoparticle based vaccine by electrostatic interaction with killed SwIAV antigen (KAg) or peptides (negative charge). Earlier we showed that Nano-11 bound killed SwIV H1N2 Ag (Nano-11+KAg) delivered intranasally in pigs induced mucosal antibody response, but the challenge heterologous H1N1 SwIV load was not substantially reduced in the airways. In this study, KAg or conserved ten IAV peptides co-adsorbed with adjuvant Poly(I:C) (negative charge) on Nano-11 [Nano-11+KAg/peptides+Poly(I:C)] was vaccinated to influenza-free pigs intranasally, twice, and challenged with a heterologous SwIV. We observed increased SIgA and IgG responses in the airways and enhanced proliferation of IFN-g+ gd T cells in PBMCs in Nano-11+KAg+Poly(I:C) vaccinates compared to control. In Nano-11+peptides+Poly(I:C) vaccinates noticed an increased proliferation of IFN-g+ gd T cells and IFN-g+ cytotoxic T cells in PBMCs compared to control. Commercial vaccine group induced higher IgG response in serum and proliferation of IFN-g+ T-helper/memory cells in PBMCs compared to control. However, reduction in challenge virus load in any of the vaccinated groups was not statistically significant. In conclusion, inclusion of Poly(I:C) in Nano-11 flu vaccine improved the T cell response, but further improvements in the vaccine formulation is required to take advantage of this easy to prepare particle based mucosal flu vaccine.

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Geng, Qibin, Wanbo Tai, Victoria K. Baxter, Juan Shi, Yushun Wan, Xiujuan Zhang, Stephanie A. Montgomery, et al. "Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection." PLOS Pathogens 17, no. 9 (September 7, 2021): e1009897. http://dx.doi.org/10.1371/journal.ppat.1009897.

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The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.

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Khandker, Shahad Saif, Brian Godman, Md Irfan Jawad, Bushra Ayat Meghla, Taslima Akter Tisha, Mohib Ullah Khondoker, Md Ahsanul Haq, et al. "A Systematic Review on COVID-19 Vaccine Strategies, Their Effectiveness, and Issues." Vaccines 9, no. 12 (November 24, 2021): 1387. http://dx.doi.org/10.3390/vaccines9121387.

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COVID-19 vaccines are indispensable, with the number of cases and mortality still rising, and currently no medicines are routinely available for reducing morbidity and mortality, apart from dexamethasone, although others are being trialed and launched. To date, only a limited number of vaccines have been given emergency use authorization by the US Food and Drug Administration and the European Medicines Agency. There is a need to systematically review the existing vaccine candidates and investigate their safety, efficacy, immunogenicity, unwanted events, and limitations. The review was undertaken by searching online databases, i.e., Google Scholar, PubMed, and ScienceDirect, with finally 59 studies selected. Our findings showed several types of vaccine candidates with different strategies against SARS-CoV-2, including inactivated, mRNA-based, recombinant, and nanoparticle-based vaccines, are being developed and launched. We have compared these vaccines in terms of their efficacy, side effects, and seroconversion based on data reported in the literature. We found mRNA vaccines appeared to have better efficacy, and inactivated ones had fewer side effects and similar seroconversion in all types of vaccines. Overall, global variant surveillance and systematic tweaking of vaccines, coupled with the evaluation and administering vaccines with the same or different technology in successive doses along with homologous and heterologous prime-booster strategy, have become essential to impede the pandemic. Their effectiveness appreciably outweighs any concerns with any adverse events.

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Xia, Ming, Pengwei Huang, Xi Jiang, and Ming Tan. "A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses." Viruses 13, no. 1 (January 6, 2021): 72. http://dx.doi.org/10.3390/v13010072.

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Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.

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Hu, Yun, Zongmin Zhao, Theresa Harmon, Paul R. Pentel, Marion Ehrich, and Chenming Zhang. "Paradox of PEGylation in fabricating hybrid nanoparticle-based nicotine vaccines." Biomaterials 182 (November 2018): 72–81. http://dx.doi.org/10.1016/j.biomaterials.2018.08.015.

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Murji, Amyn A., Juliana S. Qin, Tandile Hermanus, Lynn Morris, and Ivelin S. Georgiev. "Elicitation of Neutralizing Antibody Responses to HIV-1 Immunization with Nanoparticle Vaccine Platforms." Viruses 13, no. 7 (July 2, 2021): 1296. http://dx.doi.org/10.3390/v13071296.

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A leading strategy for developing a prophylactic HIV-1 vaccine is the elicitation of antibodies that can neutralize a large fraction of circulating HIV-1 variants. However, a major challenge that has limited the effectiveness of current vaccine candidates is the extensive global diversity of the HIV-1 envelope protein (Env), the sole target for HIV-neutralizing antibodies. To address this challenge, various strategies incorporating Env diversity into the vaccine formulation have been proposed. Here, we assessed the potential of two such strategies that utilize a nanoparticle-based vaccine platform to elicit broadly neutralizing antibody responses. The nanoparticle immunogens developed here consisted of different formulations of Envs from strains BG505 (clade A) and CZA97 (clade C), attached to the N-termini of bacterial ferritin. Single—antigen nanoparticle cocktails, as well as mosaic nanoparticles bearing both Env trimers, elicited high antibody titers in mice and guinea pigs. Furthermore, serum from guinea pigs immunized with nanoparticle immunogens achieved autologous, and in some cases heterologous, tier 2 neutralization, although significant differences between mosaic and single—antigen nanoparticles were not observed. These results provide insights into the ability of different vaccine strategies for incorporating Env sequence diversity to elicit neutralizing antibodies, with implications for the development of broadly protective HIV-1 vaccines.

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Mir, Iqra, Sania Aamir, Syed Rizwan Hussain Shah, Muhammad Shahid, Iram Amin, Samia Afzal, Amjad Nawaz, Muhammad Umer Khan, and Muhammad Idrees. "Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic." Osong Public Health and Research Perspectives 13, no. 2 (April 30, 2022): 84–100. http://dx.doi.org/10.24171/j.phrp.2022.0024.

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The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

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Zeigler, David F., Emily Gage, and Christopher H. Clegg. "Epitope-targeting platform for broadly protective influenza vaccines." PLOS ONE 16, no. 5 (May 27, 2021): e0252170. http://dx.doi.org/10.1371/journal.pone.0252170.

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Seasonal influenza vaccines are often ineffective because they elicit strain-specific antibody responses to mutation-prone sites on the hemagglutinin (HA) head. Vaccines that provide long-lasting immunity to conserved epitopes are needed. Recently, we reported a nanoparticle-based vaccine platform produced by solid-phase peptide synthesis (SPPS) for targeting linear and helical protein-based epitopes. Here, we illustrate its potential for building broadly protective influenza vaccines. Targeting known epitopes in the HA stem, neuraminidase (NA) active site, and M2 ectodomain (M2e) conferred 50–75% survival against 5LD50 influenza B and H1N1 challenge; combining stem and M2e antigens increased survival to 90%. Additionally, protein sequence and structural information were employed in tandem to identify alternative epitopes that stimulate greater protection; we report three novel HA and NA sites that are highly conserved in type B viruses. One new target in the HA stem stimulated 100% survival, highlighting the value of this simple epitope discovery strategy. A candidate influenza B vaccine targeting two adjacent HA stem sites led to >104-fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.

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Damm, Dominik, Leonardo Rojas-Sánchez, Hannah Theobald, Viktoriya Sokolova, Richard T. Wyatt, Klaus Überla, Matthias Epple, and Vladimir Temchura. "Calcium Phosphate Nanoparticle-Based Vaccines as a Platform for Improvement of HIV-1 Env Antibody Responses by Intrastructural Help." Nanomaterials 9, no. 10 (September 27, 2019): 1389. http://dx.doi.org/10.3390/nano9101389.

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Incorporation of immunodominant T-helper epitopes of licensed vaccines into virus-like particles (VLP) allows to harness T-helper cells induced by the licensed vaccines to provide intrastructural help (ISH) for B-cell responses against the surface proteins of the VLPs. To explore whether ISH could also improve antibody responses to calcium phosphate (CaP) nanoparticle vaccines we loaded the nanoparticle core with a universal T-helper epitope of Tetanus toxoid (p30) and functionalized the surface of CaP nanoparticles with stabilized trimers of the HIV-1 envelope (Env) resulting in Env-CaP-p30 nanoparticles. In contrast to soluble Env trimers, Env containing CaP nanoparticles induced activation of naïve Env-specific B-cells in vitro. Mice previously vaccinated against Tetanus raised stronger humoral immune responses against Env after immunization with Env-CaP-p30 than mice not vaccinated against Tetanus. The enhancing effect of ISH on anti-Env antibody levels was not attended with increased Env-specific IFN-γ CD4 T-cell responses that otherwise may potentially influence the susceptibility to HIV-1 infection. Thus, CaP nanoparticles functionalized with stabilized HIV-1 Env trimers and heterologous T-helper epitopes are able to recruit heterologous T-helper cells induced by a licensed vaccine and improve anti-Env antibody responses by intrastructural help.

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Joyce, M. G., Wei-Hung Chen, Rajeshwer Sankhala, Agnes Hajduczki, Paul Thomas, Elizabeth Martinez, Caroline Peterson, Mangala Rao, and Kayvon Modjarrad. "564. SARS-CoV-2 Ferritin Nanoparticle Vaccines Elicit Broad SARS Coronavirus Immunogenicity." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S384. http://dx.doi.org/10.1093/ofid/ofab466.762.

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Abstract Background The zoonotic emergence of SARS-CoV-2 quickly developed into a global pandemic. Multiple vaccine platforms have been advanced to clinical trials and emergency use authorization. The recent emergence of SARS-CoV-2 virus variants with Spike receptor-binding domain (RBD) and N-terminal domain (NTD) mutations, highlights the need for next-generation vaccines that can elicit immune responses that are resilient against Spike mutations. Methods Using a structure-based vaccine design approach, we developed multiple optimized SARS-CoV-2 nanoparticle immunogens that recapitulate the structural and antigenic profile of the SARS-CoV-2 prefusion spike. We assessed these immunogens in murine immunogenicity studies and in a K18-hACE2 transgenic mouse model with a SARS-CoV-2 challenge. Immune sera from vaccinated mice were assessed for SARS-CoV-2 binding, and neutralization against SARS-CoV-2, variants of concern, and the heterologous SARS-CoV-1 virus. Results In combination with a liposomal-saponin based adjuvant (ALFQ), these immunogens induced robust binding, ACE2-inhibition, and authentic virus and pseudovirus neutralization. A Spike-Ferritin nanoparticle (SpFN) vaccine elicited neutralizing ID50 titers >10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values >10,000 values after two immunizations. Purified antibody from SpFN- or RFN-immunized mice was transfused into K18-ACE2 transgenic mice and challenged with a high-dose SARS-CoV-2 virus stock. In order to understand the breadth of vaccine-elicited antibody responses, we analyzed SpFN- and RBD-FN-immunized animal sera against a set of heterologous SARS-CoV-2 RBD variants and SARS-CoV RBD. High binding titers with ACE2-blocking activity were observed against SARS-CoV-2 variants and the heterologous SARS-CoV-1 RBD. Furthermore, both SpFN- and RFN-immunized animal sera showed SARS-CoV-1 neutralizing ID50 titers of >2000. Conclusion These observations highlight the importance of SARS-CoV-2 neutralizing antibody levels in providing protection against emerging SARS-like coronaviruses and provide a robust platform for pandemic preparedness. Structure-based design enables development of a SARS-CoV-2 nanoparticle immunogen. Disclosures All Authors: No reported disclosures

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Nie, Ying, Lu Shi, Yanan Zhang, Yunfei Guo, and Hongchen Gu. "Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages." Cancers 14, no. 20 (October 18, 2022): 5107. http://dx.doi.org/10.3390/cancers14205107.

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Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein, we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1 phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability, while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo. Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally, we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.

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Aves, Kara-Lee, Christoph M. Janitzek, Cyrielle E. Fougeroux, Thor G. Theander, and Adam F. Sander. "Freeze-Drying of a Capsid Virus-like Particle-Based Platform Allows Stable Storage of Vaccines at Ambient Temperature." Pharmaceutics 14, no. 6 (June 18, 2022): 1301. http://dx.doi.org/10.3390/pharmaceutics14061301.

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The requirement of an undisrupted cold chain during vaccine distribution is a major economic and logistical challenge limiting global vaccine access. Modular, nanoparticle-based platforms are expected to play an increasingly important role in the development of the next-generation vaccines. However, as with most vaccines, they are dependent on the cold chain in order to maintain stability and efficacy. Therefore, there is a pressing need to develop thermostable formulations that can be stored at ambient temperature for extended periods without the loss of vaccine efficacy. Here, we investigate the compatibility of the Tag/Catcher AP205 capsid virus-like particle (cVLP) vaccine platform with the freeze-drying process. Tag/Catcher cVLPs can be freeze-dried under diverse buffer and excipient conditions while maintaining their original biophysical properties. Additionally, we show that for two model cVLP vaccines, including a clinically tested SARS-CoV-2 vaccine, freeze-drying results in a product that once reconstituted retains the structural integrity and immunogenicity of the original material, even following storage under accelerated heat stress conditions. Furthermore, the freeze-dried SARS-CoV-2 cVLP vaccine is stable for up to 6 months at ambient temperature. Our study offers a potential solution to overcome the current limitations associated with the cold chain and may help minimize the need for low-temperature storage.

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Koyande, Navami Prabhakar, Rupali Srivastava, Ananya Padmakumar, and Aravind Kumar Rengan. "Advances in Nanotechnology for Cancer Immunoprevention and Immunotherapy: A Review." Vaccines 10, no. 10 (October 16, 2022): 1727. http://dx.doi.org/10.3390/vaccines10101727.

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One of the most effective cancer therapies, cancer immunotherapy has produced outstanding outcomes in the field of cancer treatment. However, the cost is excessive, which limits its applicability. A smart way to address this issue would be to apply the knowledge gained through immunotherapy to develop strategies for the immunoprevention of cancer. The use of cancer vaccines is one of the most popular methods of immunoprevention. This paper reviews the technologies and processes that support the advantages of cancer immunoprevention over traditional cancer immunotherapies. Nanoparticle drug delivery systems and nanoparticle-based nano-vaccines have been employed in the past for cancer immunotherapy. This paper outlines numerous immunoprevention strategies and how nanotechnology can be applied in immunoprevention. To comprehend the non-clinical and clinical evaluation of these cancer vaccines through clinical studies is essential for acceptance of the vaccines.

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Berti, Cristiana, Michele Graciotti, Alice Boarino, Chakradhar Yakkala, Lana E. Kandalaft, and Harm‐Anton Klok. "Polymer Nanoparticle‐Mediated Delivery of Oxidized Tumor Lysate‐Based Cancer Vaccines." Macromolecular Bioscience 22, no. 2 (December 6, 2021): 2100356. http://dx.doi.org/10.1002/mabi.202100356.

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Doekhie, Aswin, Rajeev Dattani, Yun-Chu Chen, Francoise Koumanov, Karen J. Edler, Jean M. H. van den Elsen, and Asel Sartbaeva. "Physiochemical Changes to TTCF Ensilication Investigated Using Time-Resolved SAXS." AppliedChem 1, no. 1 (August 5, 2021): 4–13. http://dx.doi.org/10.3390/appliedchem1010002.

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Successful eradication or control of prevailing infectious diseases is linked to vaccine efficacy, stability, and distribution. The majority of protein-based vaccines are transported at fridge (2–8 °C) temperatures, cold chain, to retain potency. However, this has been shown to be problematic. Proteins are inherently susceptible to thermal fluctuations, occurring during transportation, causing them to denature. This leads to ineffective vaccines and an increase in vaccine-preventable diseases, especially in low-income countries. Our research utilises silica to preserve vaccines at room temperature, removing the need for cold chain logistics. The methodology is based upon sol–gel chemistry in which soluble silica is employed to encapsulate and ensilicate vaccine proteins. This yields a protein-loaded silica nanoparticle powder which is stored at room temperature and subsequently released using a fast chemical process. We have previously shown that tetanus toxin C fragment (TTCF) ensilication is a diffusion-limited cluster aggregation (DLCA)-based process using time-resolved small-angle x-ray scattering (SAXS). Here, we present our expanded investigation on the modularity of this system to further the understanding of ensilication via time-resolved SAXS. Our results show that variations in the ensilication process could prove useful in the transition from batch to in-flow manufacturing of ensilicated nanoparticles.

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Truong, Hannah Hanh-Hong, Waleed M. Hussein, Tzu-Yu Liu, Zhongfan Jia, James W. Wells, Michael J. Monteiro, Mariusz Skwarczynski, and Mariusz Skwarczynski. "Self-Adjuvanting Peptide Vaccines Against Cervical Cancer." Vaccination Research – Open Journal 4, no. 1 (December 31, 2019): 21–29. http://dx.doi.org/10.17140/vroj-4-114.

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Background Cervical cancer is a common cause of cancer-related deaths in women worldwide, with a fatality rate second only to breast cancer. Human papillomaviruses (HPVs) are the main causative agents of cervical cancer, and are therefore obvious targets for vaccine development. Although two prophylactic HPV vaccines have been commercialized, therapeutic vaccines against HPVs have not been developed yet. Current vaccine technologies emphasize the power of small particles in targeting immune cells, and particles of 20-50 nm have been reported to induce optimal immune responses against a variety of pathogens and cancers. Methods We synthesized new nanoparticle-based vaccines against cervical cancer by using antigenic 8Qmin peptide epitope derived from HPV-16 E7 protein, a hydrophilic poly-(L-glutamic acid) (PGA) linker, and an 8-arm poly (tert-butyl acrylate) dendrimer-based delivery system (D8). Results Four different peptides containing 8Qmin and PGA of different lengths were successfully synthesized with high yield and purity. These were then conjugated to alkyne-functionalized D8 by copper-catalyzed alkyne-azide cycloaddition “click” reaction. The conjugates self-assembled into nanoparticles, with decreased particle size corresponding to a greater number of Glu units. The four vaccine candidates were tested in C57 black 6 (C57BL/6) mice bearing well-established (7-day-old) tumors to examine their therapeutic effects. Conclusion Interestingly, only one conjugate delayed tumor growth, and montanide adjuvanted antigen, used as a positive control, failed to demonstrate any therapeutic effect.

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Sengupta, Anirban, Mohammad Azharuddin, Noha Al-Otaibi, and Jorma Hinkula. "Efficacy and Immune Response Elicited by Gold Nanoparticle- Based Nanovaccines against Infectious Diseases." Vaccines 10, no. 4 (March 24, 2022): 505. http://dx.doi.org/10.3390/vaccines10040505.

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The use of nanoparticles for developing vaccines has become a routine process for researchers and pharmaceutical companies. Gold nanoparticles (GNPs) are chemical inert, have low toxicity, and are easy to modify and functionalize, making them an attractive choice for nanovaccine development. GNPs are modified for diagnostics and detection of many pathogens. The biocompatibility and biodistribution properties of GNPs render them ideal for use in clinical settings. They have excellent immune modulatory and adjuvant properties. They have been used as the antigen carrier for the delivery system to a targeted site. Tagging them with antibodies can direct the drug or antigen-carrying GNPs to specific tissues or cells. The physicochemical properties of the GNP, together with its dynamic immune response based on its size, shape, surface charge, and optical properties, make it a suitable candidate for vaccine development. The clear outcome of modulating dendritic cells, T and B lymphocytes, which trigger cytokine release in the host, indicates GNPs’ efficiency in combating pathogens. The high titer of IgG and IgA antibody subtypes and their enhanced capacity to neutralize pathogens are reported in multiple studies on GNP-based vaccine development. The major focus of this review is to illustrate the role of GNPs in developing nanovaccines against multiple infectious agents, ranging from viruses to bacteria and parasites. Although the use of GNPs has its shortcomings and a low but detectable level of toxicity, their benefits warrant investing more thought and energy into the development of novel vaccine strategies.

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Vragniau, Charles, Joshua C. Bufton, Frédéric Garzoni, Emilie Stermann, Fruzsina Rabi, Céline Terrat, Mélanie Guidetti, et al. "Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display." Science Advances 5, no. 9 (September 2019): eaaw2853. http://dx.doi.org/10.1126/sciadv.aaw2853.

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Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. We used cryo–electron microscopy at near-atomic resolution and implemented novel, cost-effective, high-performance cloud computing to reveal architectural features in unprecedented detail. We analyzed ADDomer interaction with components of the immune system and developed a promising first-in-kind ADDomer-based vaccine candidate to combat emerging Chikungunya infectious disease, exemplifying the potential of our approach.

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Zhao, Kai, Yinzhuo Xie, Xuezheng Lin, and Wei Xu. "The Mucoadhesive Nanoparticle-Based Delivery System in the Development of Mucosal Vaccines." International Journal of Nanomedicine Volume 17 (September 2022): 4579–98. http://dx.doi.org/10.2147/ijn.s359118.

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Chan, Yinghan, Sin Wi Ng, Sachin Kumar Singh, Monica Gulati, Gaurav Gupta, Sushil Kumar Chaudhary, Goh Bey Hing, et al. "Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective." Life Sciences 280 (September 2021): 119744. http://dx.doi.org/10.1016/j.lfs.2021.119744.

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Brito Baleeiro, R., M. Schweinlin, R. Rietscher, A. Diedrich, J. A. Czaplewska, M. Metzger, C. Michael Lehr, et al. "Nanoparticle-Based Mucosal Vaccines Targeting Tumor-Associated Antigens to Human Dendritic Cells." Journal of Biomedical Nanotechnology 12, no. 7 (July 1, 2016): 1527–43. http://dx.doi.org/10.1166/jbn.2016.2267.

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Renukaradhya, Gourapura J., Balaji Narasimhan, and Surya K. Mallapragada. "Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation." Journal of Controlled Release 219 (December 2015): 622–31. http://dx.doi.org/10.1016/j.jconrel.2015.09.047.

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Lin, Leon Chien-Wei, Saborni Chattopadhyay, Jung-Chen Lin, and Che-Ming Jack Hu. "Advances and Opportunities in Nanoparticle- and Nanomaterial-Based Vaccines against Bacterial Infections." Advanced Healthcare Materials 7, no. 13 (March 6, 2018): 1701395. http://dx.doi.org/10.1002/adhm.201701395.

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Björgvinsdóttir, Unnur Jóna, Laura Stentoft Carstensen, Anna Colliander, Ditte Elisabeth Jæhger, Gael Clergeaud Veiga, Hólmfríður Rósa Halldórsdóttir, Matilde Smærup Jørgensen, et al. "771 Novel lipid nanoparticle vaccine platform for efficient delivery of high- and low-affinity epitopes." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A806. http://dx.doi.org/10.1136/jitc-2021-sitc2021.771.

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BackgroundTherapeutic cancer vaccines represent an intriguing approach to cancer immunotherapy and they have been widely explored for the last decade. As opposed to standard modalities, such as surgery and chemotherapy, an effective vaccine-based immune response may provide protection against metastatic disease. Peptide based vaccines can elicit a highly targeted immune response and include a simple, fast and cost-effective production due to recent developments in solid phase peptide synthesis. Recent development within the field of COVID-19 vaccines has highlighted the use of lipid nanoparticles as an effective drug delivery system for vaccination. Incorporation of peptide antigens into engineered micro- and nanoparticles enables induction of a potent T cell response, partly attributed to prolonged and improved antigen presentation by dendritic cells after particle internalization. Peptide-based vaccines are often based on delivery of high-affinity T cell model epitopes. However, the therapeutic relevance of vaccination with low-affinity epitopes is gaining increasing support following the observation that high-affinity epitopes can promote T cell exhaustion resulting from excessive T cell receptor stimulation. Here, we characterize and evaluate a novel lipid nanoparticle (LNP) vaccine platform that is suited for delivery of both high- and low-affinity epitopes in the setting of therapeutic cancer vaccination.MethodsLNPs were formulated to carry high- or low-affinity peptide epitopes from Ovalbumin (OVA) in conjunction with the TLR7 agonist 1V270. The peptides were anchored to the surface of the LNPs via a reducible DSPE-PEG2000 linker system. The therapeutic vaccine platform was evaluated in vivo both as a monotherapy and in combination with adoptive transfer of OT-I T cells in the syngeneic B16-OVA murine melanoma model.ResultsThe LNP vaccine promotes efficient antigen-release and ensures high, continuous antigen-presentation by antigen-presenting cells. While the LNPs can be administered via multiple routes, intratumoral vaccination favors enhanced particle uptake in dendritic cells in the tumor. Formulated with either high- or low-affinity epitopes, intratumorally delivered vaccine particles promote superior tumor-infiltration of adoptively transferred T cells, which translates into potent anti-tumor efficacy in vivo. Finally, we show that vaccination with both CD8+ and CD4+ epitopes can delay tumor growth and prolong survival in an antigen-dependent manner.ConclusionsThis study presents a versatile and multi-purpose LNP vaccine platform that ensures effective delivery of high- and low-affinity epitopes. Intratumoral administration promotes vaccine particle uptake by intratumoral dendritic cells, which is followed by T cell infiltration and anti-tumor efficacy in vivo.Ethics ApprovalAll animal procedures were approved by the Danish National Animal Experiments Inspectorate.

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Lundstrom, Kenneth. "Viral Vectors for COVID-19 Vaccine Development." Viruses 13, no. 2 (February 19, 2021): 317. http://dx.doi.org/10.3390/v13020317.

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Vaccine development against SARS-CoV-2 has been fierce due to the devastating COVID-19 pandemic and has included all potential approaches for providing the global community with safe and efficient vaccine candidates in the shortest possible timeframe. Viral vectors have played a central role especially using adenovirus-based vectors. Additionally, other viral vectors based on vaccinia viruses, measles viruses, rhabdoviruses, influenza viruses and lentiviruses have been subjected to vaccine development. Self-amplifying RNA virus vectors have been utilized for lipid nanoparticle-based delivery of RNA as COVID-19 vaccines. Several adenovirus-based vaccine candidates have elicited strong immune responses in immunized animals and protection against challenges in mice and primates has been achieved. Moreover, adenovirus-based vaccine candidates have been subjected to phase I to III clinical trials. Recently, the simian adenovirus-based ChAdOx1 vector expressing the SARS-CoV-2 S spike protein was approved for use in humans in the UK.

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Barnowski, Cornelia, Nicole Kadzioch, Dominik Damm, Huimin Yan, and Vladimir Temchura. "Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines." Pharmaceutics 11, no. 5 (May 1, 2019): 204. http://dx.doi.org/10.3390/pharmaceutics11050204.

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The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity.

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Miao, Jing, Peng Gao, Qian Li, Kaifeng He, Liwen Zhang, Junyan Wang, and Lingfei Huang. "Advances in Nanoparticle Drug Delivery Systems for Anti-Hepatitis B Virus Therapy: A Narrative Review." International Journal of Molecular Sciences 22, no. 20 (October 18, 2021): 11227. http://dx.doi.org/10.3390/ijms222011227.

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Chronic hepatitis B (CHB) is an infectious viral disease that is prevalent worldwide. Traditional nucleoside analogues, as well as the novel drug targets against hepatitis B virus (HBV), are associated with certain critical factors that influence the curative effect, such as biological stability and safety, effective drug delivery, and controlled release. Nanoparticle drug delivery systems have significant advantages and have provided a basis for the development of anti-HBV strategies. In this review, we aim to review the advances in nanoparticle drug delivery systems for anti-hepatitis B virus therapy by summarizing the relevant literature. First, we focus on the characteristics of nanoparticle drug delivery systems for anti-HBV therapy. Second, we discuss the nanoparticle delivery systems for anti-HBV nucleoside drugs, gene-based drugs, and vaccines. Lastly, we provide an overview of the prospects for nanoparticle-based anti-HBV agents.

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Journal articles on the topic 'Nanoparticle-based vaccines'

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