Durability and Cross-Reactivity of Immune Responses Induced by an AS03 Adjuvanted Plant-Based Recombinant Virus-Like Particle Vaccine for COVID-19

As the SARS-COV-2 pandemic evolves, what is expected of vaccines extends beyond efficacy to include consideration of both durability and variant cross-reactivity. This report expands on previously reported immunogenicity results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults 18-49 years of age (NCT04450004). When humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201), 100% of vaccinated individuals retained binding antibodies, and [~]95% retained neutralizing antibodies; interferon gamma (IFN-{gamma}) and interleukin 4 (IL-4) responses directed against the ancestral S protein were also still detectable in [~]94% and [~]92% of vaccinees respectively. Variant-specific, cross-reactive neutralizing antibody (NAb) levels were assessed at D42 and D201 using both live wild-type and pseudovirion assays (Alpha, Beta, Gamma) or the wild-type assay alone (Delta, Omicron). In the wild-type assay, broad cross-reactivity was detected against all variants at D42 (100% Alpha and Delta, 94% Beta and Gamma, 74% Omicron). At D201, cross-reactive antibodies were detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results were similar in the pseudovirion assay (D42, 100% cross-reactivity to Alpha and Gamma variants, 95% to Beta variant, D201, 94% for Alpha, Beta and Gamma variants). These data suggest that two doses of 3.75 {micro}g CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination.