TY - JOUR T1 - Protein Vaccine Induces a Durable, More Broadly Neutralizing Antibody Response in Macaques than Natural Infection with SARS-CoV-2 P.1 JF - bioRxiv DO - 10.1101/2021.09.24.461759 SP - 2021.09.24.461759 AU - Albert To AU - Teri Ann S. Wong AU - Michael M. Lieberman AU - Karen Thompson AU - Laurent Pessaint AU - Jack Greenhouse AU - Nisrine Daham AU - Anthony Cook AU - Brandon Narvaez AU - Zack Flinchbaugh AU - Alex Van Ry AU - Jake Yalley-Ogunro AU - Hanne Andersen Elyard AU - Chih-Yun Lai AU - Oreola Donini AU - Axel T. Lehrer Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/25/2021.09.24.461759.abstract N2 - FDA-approved and Emergency Use Authorized (EUA) 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 SARS-CoV-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], B.1.617 [Delta]) for at least 3 months after the final boost. Protective efficacy and post-exposure immunity were evaluated using a heterologous P.1 challenge nearly 3 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. Post-challenge 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 (non-vaccinated 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 long-lasting and protective immunity against circulating VOCs.One Sentence Summary A recombinant subunit protein formulated with CoVaccine HT™ adjuvant induces superior immunity than natural infection and reduces viral load while protecting cynomolgus macaques from COVID-19-like disease caused by late SARS-CoV-2 P.1 (Gamma) challenge.Competing Interest StatementATL and OD are named inventors on a patent application covering a recombinant subunit vaccine for SARS-CoV-2. LP, JG, ND, AC, BN, ZF, AVR, JYO and HA are current employees of BIOQUAL, Inc. OD is a current employee of Soligenix Inc. All other authors declare no competing interests. ER -