Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice
Autor: | Shivani Mody, Patricia Spilman, Kyle Dinkins, Kayvan Niazi, Annie Shin, Adrian Rice, Brett Morimoto, Helty Adisetiyo, Lise Zakin, Jeffrey T. Safrit, Shiho Tanaka, Shahrooz Rabizadeh, Elizabeth Gabitzsch, Peter A. Sieling, Joseph P. Balint, C. Anders Olson, Wendy Higashide, Patrick Soon-Shiong, Mohit Verma |
---|---|
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
COVID-19 Vaccines Science T cell Immunology Genetic Vectors Immunization Secondary Mice Inbred Strains Antibodies Viral medicine.disease_cause Article Adenoviridae Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Immunity medicine Animals Immunity Mucosal Administration Intranasal Immunity Cellular Multidisciplinary biology Drug discovery SARS-CoV-2 Vaccination COVID-19 Hypodermoclysis Antibodies Neutralizing 030104 developmental biology medicine.anatomical_structure Immunization 030220 oncology & carcinogenesis biology.protein Medicine Female Antibody |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses. Finally, we used a combined SC plus IN (SC + IN) prime with or without a boost and found the SC + IN prime alone to be as effective in generating humoral and T-cell responses as the SC + IN prime with a boost. The finding that SC + IN prime-only delivery has the potential to provide broad immunity—including mucosal immunity—against SARS-CoV-2 supports further testing of this vaccine and delivery approach in animal models of viral challenge. |
Databáze: | OpenAIRE |
Externí odkaz: |