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.
Keywords: COVID-19; SARS-CoV-2 challenge; dual antigen; lung; nasal passages; non-human primate (NHP); protection; vaccine.
Copyright © 2021 Gabitzsch, Safrit, Verma, Rice, Sieling, Zakin, Shin, Morimoto, Adisetiyo, Wong, Bezawada, Dinkins, Balint, Peykov, Garban, Liu, Bacon, Bone, Drew, Sanford, Spilman, Sender, Rabizadeh, Niazi and Soon-Shiong.