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.
Keywords: CoVaccine HT; SARS-CoV-2; cynomolgus macaques; delayed challenge; lyophilized; subunit protein vaccine.
【저자키워드】 SARS-CoV-2, cynomolgus macaques, CoVaccine HT, delayed challenge, lyophilized, subunit protein vaccine., 【초록키워드】 neutralizing antibody, IgG, Efficacy, Vaccine, coronavirus, pandemic, Immunity, Neutralizing antibodies, VoC, B.1.351, Infection, variants of concern, severe acute respiratory syndrome Coronavirus, immunization, Antigen, Protein, Reinfection, Viral, Viral load, protective immunity, mRNA, P.1, B.1.617, VOCs, Beta, Subunit vaccine, macaque, respiratory, information, natural infection, disease, moderate, anamnestic response, Neutralizing antibody response, Heterologous, boost, cynomolgus macaques, Protective, breadth, macaques, Lung pathology, Concentration, dose, severe disease, isolates, Lower respiratory tract, moderate to severe, acute respiratory syndrome, subunit, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, viral loads, Final, immunogenic, circulating, upper and lower respiratory tract, liquid, specific neutralizing antibodies, vaccine immunity, Prevent, effective, immunized, robust, significantly, evaluated, required, elevated, induce, cause, reduce, restored, dosed, 【제목키워드】 P.1, response, Gamma, macaque, potent, recombinant, the SARS-CoV-2,