A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant br

FDA-approved and emergency use-authorized vaccines using new mRNA and viral-vector technology are highlyeffective in preventing moderate to severe disease; however, information on their long-term efficacy and protective breadth againstsevere acute respiratory syndrome coronavirus 2 variants of concern (VOCs) is currently scarce. Here, we describe the durability andbroad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT incynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadlyneutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], and B.1.617 [Delta]) for at leastthree months after thefinal boost. Protective efficacy and postexposure immunity were evaluated using a heterologous P.1 challengenearly three months after the last immunization. Our results indicate that while immunization with both high and low S dosesshorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durableprotection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology asseen with early pandemic isolates. Postchallenge IgG concentrations were restored to peak immunity levels, and vaccine-matchedand cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnesticresponse. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (nonvaccinated butchallenged) macaques, suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these resultsdemonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide protective immunity against circulatingVOCs for at least three months.