1. A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant.
- Author
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To A, Wong TAS, Lieberman MM, Thompson K, Ball AH, Pessaint L, Greenhouse J, Daham N, Cook A, Narvaez B, Flinchbaugh Z, Van Ry A, Yalley-Ogunro J, Andersen Elyard H, Lai CY, Donini O, and Lehrer AT
- Subjects
- Adjuvants, Immunologic, Animals, Antibodies, Neutralizing, Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, Macaca, Vaccines, Subunit, COVID-19 prevention & control, SARS-CoV-2
- Abstract
FDA-approved and emergency use-authorized vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease; however, information on their long-term efficacy and protective breadth against severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) is currently scarce. Here, we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], and B.1.617 [Delta]) for at least three months after the final boost. Protective efficacy and postexposure immunity were evaluated using a heterologous P.1 challenge nearly three months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Postchallenge IgG concentrations were restored to peak immunity levels, and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (nonvaccinated but challenged) macaques, suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide protective immunity against circulating VOCs for at least three months.
- Published
- 2022
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