tetano
Editor, Senior Moderator
J Immunol
. 2022 Jun 24;ji2200056.
doi: 10.4049/jimmunol.2200056. Online ahead of print.
Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1
Gina M Cusimano[SUP] 1 2 [/SUP], Ebony N Gary[SUP] 3 [/SUP], Matthew R Bell[SUP] 1 2 [/SUP], Bryce M Warner[SUP] 4 [/SUP], Jennifer Connors[SUP] 1 2 [/SUP], Nicholas J Tursi[SUP] 3 [/SUP], Ali R Ali[SUP] 3 [/SUP], Shiyu Zhang[SUP] 5 [/SUP], Gabriela Canziani[SUP] 5 [/SUP], Bhavani Taramangalam[SUP] 1 [/SUP], Emma A Gordon[SUP] 2 [/SUP], Irwin M Chaiken[SUP] 5 [/SUP], Sarah K Wootton[SUP] 6 [/SUP], Trevor Smith[SUP] 7 [/SUP], Stephanie Ramos[SUP] 7 [/SUP], Darwyn Kobasa[SUP] 4 8 [/SUP], David B Weiner[SUP] 3 [/SUP], Michele A Kutzler[SUP] 9 2 [/SUP], Elias K Haddad[SUP] 9 2 [/SUP]
Affiliations
Abstract
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.
. 2022 Jun 24;ji2200056.
doi: 10.4049/jimmunol.2200056. Online ahead of print.
Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1
Gina M Cusimano[SUP] 1 2 [/SUP], Ebony N Gary[SUP] 3 [/SUP], Matthew R Bell[SUP] 1 2 [/SUP], Bryce M Warner[SUP] 4 [/SUP], Jennifer Connors[SUP] 1 2 [/SUP], Nicholas J Tursi[SUP] 3 [/SUP], Ali R Ali[SUP] 3 [/SUP], Shiyu Zhang[SUP] 5 [/SUP], Gabriela Canziani[SUP] 5 [/SUP], Bhavani Taramangalam[SUP] 1 [/SUP], Emma A Gordon[SUP] 2 [/SUP], Irwin M Chaiken[SUP] 5 [/SUP], Sarah K Wootton[SUP] 6 [/SUP], Trevor Smith[SUP] 7 [/SUP], Stephanie Ramos[SUP] 7 [/SUP], Darwyn Kobasa[SUP] 4 8 [/SUP], David B Weiner[SUP] 3 [/SUP], Michele A Kutzler[SUP] 9 2 [/SUP], Elias K Haddad[SUP] 9 2 [/SUP]
Affiliations
- PMID: 35750334
- DOI: 10.4049/jimmunol.2200056
Abstract
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.