1960. Mucosal rAd5 Immunization against SARS-CoV-2 Spike Elicits Cross-Reactive Nasal and Serum Neutralizing Antibodies and Protects Against Beta Variant Challenge in African Green Monkeys

Abstract Background Mucosal vaccination may offer increased protection against SARS-CoV-2 compared to parental immunization. Here, we describe immunogenicity and efficacy following viral challenge in non-human primates after intranasal delivery of three unique non-replicating adenoviral vector vaccine (rAd5) candidates. Methods African green monkeys (AMG) were prime boost immunized 29 days apart with vaccine candidates either expressing the parental spike protein alone (Wuhan-S), spike plus nucleocapsid (Wuhan-S-N), or the spike protein from the beta variant (beta-S). Serum and nasal swabs were collected every 14 days and humoral responses to full length spike (S) and receptor binding domain (RBD) were assessed. All AMGs were challenged with SARS-CoV-2 B.1.351 (beta variant) on day 56. Viral loads measured every two days by TCID50 in nasal washes and bronchial lavage fluid post challenge. Results Mucosal immunization with Wuhan-S induced significant increases in serum IgG and IgA responses against the homologous parental lineage, as well as beta, delta, and omicron variants. In nasal samples, Wuhan-S immunization elicited over 500-fold increases in in cross-reactive IgA against multiple variants of concern including delta and omicron. While the beta-S rAd5 vaccine candidate induced enhanced serum IgG responses to homologous S and RBD proteins, this approach resulted in less cross-reactive antibodies to other variants compared to Wuhan-S rAd5 vaccine. Despite the differences in the ability to elicit cross-reactive antibody responses, all vaccinated AMGs challenged with SARS-CoV-2 B.1.351 (beta variant), had a significant reduction in viral titers by TCID50 in the nasal passages and reduced viral load in bronchial lavage fluid compared to unvaccinated controls. Conclusion These results demonstrate mucosal administration of rAd5 clinical candidate vaccine, Wuhan-S, is immunogenic and offers cross-protective humoral responses in both serum and nasal compartments against a mismatched SARS-CoV-2 challenge virus. Disclosures Becca A. Flitter, PhD, MPH, Vaxart Inc: Stocks/Bonds Sarah N. Tedjakusuma, n/a, Vaxart Inc: Stocks/Bonds Colin A. Lester, n/a, Vaxart Inc: Stocks/Bonds Elena D. Neuhaus, n/a, Vaxart Inc: Stocks/Bonds Susan Johnson, PhD, Vaxart Inc: Stocks/Bonds Emery G. Dora, n/a, Vaxart Inc: Stocks/Bonds Nadine Peinovich, MPH, Vaxart Inc: Stocks/Bonds Clara B. Jegede, n/a, Vaxart Inc: Stocks/Bonds Sean N. Tucker, PhD, Vaxart Inc: Stocks/Bonds.