Affiliation:
1. Bharat Biotech International Ltd, Hyderabad, India
Abstract
Abstract
Most if not all vaccine candidates developed to combat COVID-19 due to SARS-CoV-2 infection are administered parenterally. As SARS-CoV-2 is transmitted through infectious respiratory fluids, vaccine-induced mucosal immunity could provide an important contribution to control this pandemic. ChAd-SARS-CoV-2-S (BBV154), a replication-defective chimpanzee adenovirus (ChAd)-vectored intranasal (IN) COVID-19 vaccine candidate, encodes a prefusion-stabilized version of the SARS-CoV-2 spike protein containing two proline substitutions in the S2 subunit. We performed preclinical evaluations of BBV154 in mice, rats, hamsters and rabbits. Repeated dose toxicity studies presented excellent safety profiles in terms of pathology and biochemical analysis. IN administration of BBV154 elicited robust mucosal and systemic humoral immune responses coupled with cell-mediated immune responses dominated by Th1-like cytokine expression. Heterologous prime-boost vaccination with intramuscular (IM) COVAXIN-prime followed by BBV154 intranasal in rabbits elicited superior immune responses compared with the homologous COVAXIN/COVAXIN schedule. BBV154 is now being assessed in both homologous and heterologous combination schedules in ongoing human clinical trials.
Publisher
Research Square Platform LLC
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