Complete Protection of Nasal and Lung Airways Against SARS-CoV-2 Challenge by Antibody Plus Th1 Dominant N- and S-Specific T-Cell Responses to Subcutaneous Prime and Thermally-Stable Oral Boost Bivalent hAd5 Vaccination in an NHP Study

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; Bone, Pete; Bacon, Andrew; Drew, Jeff; Sanford, Daniel C.; Spilman, Patricia; Sender, Lennie; Rabizadeh, Shahrooz; Niazi, Kayvan; Soon-Shiong, Patrick

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike (S-Fusion) protein and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) with the potential to increase MHC class I/II responses. The adenovirus serotype 5 platform used, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity, can be delivered in an oral formulation that overcomes cold-chain limitations. The hAd5 S-Fusion + N-ETSD vaccine was evaluated in rhesus macaques showing that a subcutaneous prime followed by oral boosts elicited both humoral and Th1 dominant 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. ONE SENTENCE SUMMARY hAd5 spike + nucleocapsid SC prime/oral boost vaccine elicits humoral and T-cell responses and protects rhesus macaques from SARS-CoV-2 challenge.