J Immunol . Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1

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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 ^{1 2} , Ebony N Gary ³ , Matthew R Bell ^{1 2} , Bryce M Warner ⁴ , Jennifer Connors ^{1 2} , Nicholas J Tursi ³ , Ali R Ali ³ , Shiyu Zhang ⁵ , Gabriela Canziani ⁵ , Bhavani Taramangalam ¹ , Emma A Gordon ² , Irwin M Chaiken ⁵ , Sarah K Wootton ⁶ , Trevor Smith ⁷ , Stephanie Ramos ⁷ , Darwyn Kobasa ^{4 8} , David B Weiner ³ , Michele A Kutzler ^{9 2} , Elias K Haddad ^{9 2}



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.