Lenart K, Arcoverde Cerveira R, Hellgren F, Ols S, Sheward DJ, Kim C, Cagigi A, Gagne M, Davis B, Germosen D, Roy V, Alter G, Letscher H, Van Wassenhove J, Gros W, Gallouët A, Le Grand R, Kleanthous H, Guebre-Xabier M, Murrell B, Patel N, Glenn G, Smith G, Loré K
NPJ Vaccines 9 (1) 17 [2024-01-20; online 2024-01-20]
The immune responses to Novavax's licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-MTM adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery. A third dose of an updated vaccine based on the Gamma (P.1) variant 7 months after two immunizations with licensed NVX-CoV2373 resulted in significant enhancement of anti-spike antibody titers and antibody breadth including neutralization of forward drift Omicron variants. The third immunization expanded the Spike-specific memory B cell pool, induced significant somatic hypermutation, and increased serum antibody avidity, indicating considerable affinity maturation. Seven months after immunization, vaccinated animals controlled infection by either WA-1 or P.1 strain, mediated by rapid anamnestic antibody and T cell responses in the lungs. In conclusion, a third immunization with an adjuvanted, low-dose recombinant protein vaccine significantly improved the quality of B cell responses, enhanced antibody breadth, and provided durable protection against SARS-CoV-2 challenge.