Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge
Elizabeth Gabitzsch, Jeffrey T. Safrit, Mohit S. Verma, Adrian Rice, Peter A. Sieling, Lise Zakin, Annie Shin, Brett Morimoto, Helty Adisetiyo, Raymond M.H. Wong, Ashish Bezawada, Kyle Dinkins, Joseph P. Balint, Victor Peykov, Hermes Garbán, Philip L.‐F. Liu, Andrew Bacon, Pete Bone, Jeff Drew, Daniel Sanford, Patricia Spilman, Lennie Sender, Shahrooz Rabizadeh, Kayvan Niazi, Patrick Soon‐Shiong
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 10 6 TCID 50 ) 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.