Intranasal replicating adenovirus type 4-SARS-CoV-2 recombinants induce durable immunity in hamsters 3142

Abstract Description The portfolio of next generation COVID-19 vaccines would benefit from candidates that induce a durable systemic and mucosal immune response. Vaccination at the site of infection is expected to produce mucosal immunity, better protecting against COVID-19 infection and reducing person-to-person transmission. In prior clinical trials, a single intranasal dose of a replication-competent Ad4 recombinant expressing influenza hemagglutinin (H5) induced durable systemic and mucosal immune responses. We adapted this vaccine platform to express SARS-CoV-2 Spike variants and assessed immunogenicity and efficacy in the Syrian golden hamster model. Although both intranasal Ad4 recombinants and intramuscular vaccines (Ad26.CoV2.S and mRNA-1273) induced Spike-binding serum Ig, only Ad4 recombinants induced such responses in the nasal cavity. Intranasal vaccination with Ad4-Spike recombinants additionally induced serum neutralizing titers that were equivalent to intramuscular vaccination with mRNA-1273 but offered considerably greater durability up to 6 months post-vaccination. Upon challenge, intranasal immunization also resulted in reduced weight loss, greater restriction of viral replication, and lower levels of lung pathology compared to intramuscular immunization. Together, these data add to a growing body of evidence that suggests that a replication-competent, intranasal vaccine platform offers key features that could be critical in fighting COVID-19 and future pandemics. Funding Sources Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases Topic Categories Vaccines and Immunotherapy (VAC)