Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge
Autor: | Jeff Drew, Raymond C.B. Wong, Brett Morimoto, Shahrooz Rabizadeh, Peter A. Sieling, Lennie Sender, Pete Bone, Daniel C. Sanford, Patrick Soon-Shiong, Andrew Bacon, Victor Peykov, Patricia Spilman, Adrian Rice, Jeffrey T. Safrit, Mohit Verma, Lise Zakin, Joseph P. Balint, Kyle Dinkins, Hermes Garban, Ashish Bezawada, Kayvan Niazi, Annie Shin, Philip T. Liu, Helty Adisetiyo, Elizabeth Gabitzsch |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
COVID-19 Vaccines
Immunology Immunization Secondary Administration Oral dual antigen Nose Antibodies Viral Virus Replication Immunoglobulin G lung Protein Domains Antigen Immunity vaccine medicine Animals Coronavirus Nucleocapsid Proteins Immunology and Allergy Original Research nasal passages MHC class II biology SARS-CoV-2 business.industry Adenoviruses Human Vaccination Viral nucleocapsid COVID-19 T-Lymphocytes Helper-Inducer T helper cell RC581-607 Phosphoproteins SARS-CoV-2 challenge protection Antibodies Neutralizing Macaca mulatta Virology non-human primate (NHP) medicine.anatomical_structure Viral replication Spike Glycoprotein Coronavirus biology.protein Cytokines Immunologic diseases. Allergy business |
Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
ISSN: | 1664-3224 |
DOI: | 10.3389/fimmu.2021.729837/full |
Popis: | We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge. |
Databáze: | OpenAIRE |
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