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

• Published in: bioRxiv
• Main Authors: 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
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 26.03.2021
• Subjects: COVID-19; COVID-19 vaccines; Fusion protein; Lymphocytes T; Major histocompatibility complex; Nucleocapsids; Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccines
• DOI: 10.1101/2020.12.08.416297

ABSTRACT 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 hAd5 spike + nucleocapsid SC prime/oral boost vaccine elicits humoral and T-cell responses and protects rhesus macaques from SARS-CoV-2 challenge. Competing Interest Statement Authors with ImmunityBio LLC or NantKwest Inc affiliations have participated in the design, manufacture or testing of the hAd5 S-Fusion + N-ETSD vaccine. Dr. Soon-Shiong is Chairman and CEO of NantKwest and CEO of ImmunityBio Footnotes * Pete Bone of IosBio, Inc. has been added as an author and Phil Yang of ImmunityBio has been thanked in Acknowledgements