tetano
Editor, Senior Moderator
ACS Infect Dis
. 2022 Mar 9.
doi: 10.1021/acsinfecdis.1c00600. Online ahead of print.
A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant
Albert To[SUP] 1 [/SUP], Teri Ann S Wong[SUP] 1 [/SUP], Michael M Lieberman[SUP] 1 [/SUP], Karen Thompson[SUP] 2 [/SUP], Aquena H Ball[SUP] 1 [/SUP], Laurent Pessaint[SUP] 3 [/SUP], Jack Greenhouse[SUP] 3 [/SUP], Nisrine Daham[SUP] 3 [/SUP], Anthony Cook[SUP] 3 [/SUP], Brandon Narvaez[SUP] 3 [/SUP], Zack Flinchbaugh[SUP] 3 [/SUP], Alex Van Ry[SUP] 3 [/SUP], Jake Yalley-Ogunro[SUP] 3 [/SUP], Hanne Andersen Elyard[SUP] 3 [/SUP], Chih-Yun Lai[SUP] 1 [/SUP], Oreola Donini[SUP] 4 [/SUP], Axel T Lehrer[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Mar 9.
doi: 10.1021/acsinfecdis.1c00600. Online ahead of print.
A Recombinant Subunit Vaccine Induces a Potent, Broadly Neutralizing, and Durable Antibody Response in Macaques against the SARS-CoV-2 P.1 (Gamma) Variant
Albert To[SUP] 1 [/SUP], Teri Ann S Wong[SUP] 1 [/SUP], Michael M Lieberman[SUP] 1 [/SUP], Karen Thompson[SUP] 2 [/SUP], Aquena H Ball[SUP] 1 [/SUP], Laurent Pessaint[SUP] 3 [/SUP], Jack Greenhouse[SUP] 3 [/SUP], Nisrine Daham[SUP] 3 [/SUP], Anthony Cook[SUP] 3 [/SUP], Brandon Narvaez[SUP] 3 [/SUP], Zack Flinchbaugh[SUP] 3 [/SUP], Alex Van Ry[SUP] 3 [/SUP], Jake Yalley-Ogunro[SUP] 3 [/SUP], Hanne Andersen Elyard[SUP] 3 [/SUP], Chih-Yun Lai[SUP] 1 [/SUP], Oreola Donini[SUP] 4 [/SUP], Axel T Lehrer[SUP] 1 [/SUP]
Affiliations
- PMID: 35263081
- DOI: 10.1021/acsinfecdis.1c00600
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.