Artificial Cell Membrane Polymersome-Based Intranasal Beta Spike Formulation as a Second Generation Covid-19 Vaccine
العنوان: | Artificial Cell Membrane Polymersome-Based Intranasal Beta Spike Formulation as a Second Generation Covid-19 Vaccine |
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المؤلفون: | Jian Hang Lam, Devendra Shivhare, Teck Wan Chia, Suet Li Chew, Gaurav Sinsinbar, Ting Yan Aw, Siamy Wong, Shrinivas Venkataraman, Francesca Wei Inng Lim, Pierre Vandepapeliere, Madhavan Nallani |
المصدر: | ACS Nano. 16:16757-16775 |
بيانات النشر: | American Chemical Society (ACS), 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | COVID-19 Vaccines, SARS-CoV-2, General Engineering, COVID-19, General Physics and Astronomy, Membranes, Artificial, Antibodies, Viral, Antibodies, Neutralizing, Mice, Inbred C57BL, Mice, Cricetinae, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Humans, Animals, Artificial Cells, General Materials Science, Rabbits |
الوصف: | Current parenteral coronavirus disease 2019 (Covid-19) vaccines inadequately protect against infection of the upper respiratory tract. Additionally, antibodies generated by wild type (WT) spike-based vaccines poorly neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. To address the need for a second-generation vaccine, we have initiated a preclinical program to produce and evaluate a potential candidate. Our vaccine consists of recombinant Beta spike protein coadministered with synthetic CpG adjuvant. Both components are encapsulated within artificial cell membrane (ACM) polymersomes, synthetic nanovesicles efficiently internalized by antigen presenting cells, including dendritic cells, enabling targeted delivery of cargo for enhanced immune responses. ACM vaccine is immunogenic in C57BL/6 mice and Golden Syrian hamsters, evoking high serum IgG and neutralizing responses. Compared to an ACM-WT spike vaccine that generates predominantly WT-neutralizing antibodies, the ACM-Beta spike vaccine induces antibodies that neutralize WT and Beta viruses equally. Intramuscular (IM)-immunized hamsters are strongly protected from weight loss and other clinical symptoms after the Beta challenge but show delayed viral clearance in the upper airway. With intranasal (IN) immunization, however, neutralizing antibodies are generated in the upper airway concomitant with rapid and potent reduction of viral load. Moreover, antibodies are cross-neutralizing and show good activity against Omicron. Safety is evaluated in New Zealand white rabbits in a repeated dose toxicological study under Good Laboratory Practice (GLP) conditions. Three doses, IM or IN, at two-week intervals do not induce an adverse effect or systemic toxicity. Cumulatively, these results support the application for a Phase 1 clinical trial of ACM-polymersome-based Covid-19 vaccine (ClinicalTrials.gov identifier: NCT05385991). |
تدمد: | 1936-086X 1936-0851 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88407cb9c299c25314d967663eb1a0ce https://doi.org/10.1021/acsnano.2c06350 |
حقوق: | CLOSED |
رقم الأكسشن: | edsair.doi.dedup.....88407cb9c299c25314d967663eb1a0ce |
قاعدة البيانات: | OpenAIRE |
تدمد: | 1936086X 19360851 |
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