AUTHOR=Gabitzsch Elizabeth , Safrit Jeffrey T. , Verma Mohit , Rice Adrian , Sieling Peter , Zakin Lise , Shin Annie , Morimoto Brett , Adisetiyo Helty , Wong Raymond , Bezawada Ashish , Dinkins Kyle , Balint Joseph , Peykov Victor , Garban Hermes , Liu Philip , Bacon Andrew , Bone Pete , Drew Jeff , Sanford Daniel C. , Spilman Patricia , Sender Lennie , Rabizadeh Shahrooz , Niazi Kayvan , Soon-Shiong Patrick TITLE=Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.729837 DOI=10.3389/fimmu.2021.729837 ISSN=1664-3224 ABSTRACT=

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.