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

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 deamina...

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Published inThe Journal of immunology (1950) Vol. 209; no. 1; pp. 118 - 127
Main Authors Cusimano, Gina M, Gary, Ebony N, Bell, Matthew R, Warner, Bryce M, Connors, Jennifer, Tursi, Nicholas J, Ali, Ali R, Zhang, Shiyu, Canziani, Gabriela, Taramangalam, Bhavani, Gordon, Emma A, Chaiken, Irwin M, Wootton, Sarah K, Smith, Trevor, Ramos, Stephanie, Kobasa, Darwyn, Weiner, David B, Kutzler, Michele A, Haddad, Elias K
Format Journal Article
LanguageEnglish
Published United States 01.07.2022
Subjects
Adenosine Deaminase - genetics
Adjuvants, Immunologic
Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 - prevention & control
COVID-19 Vaccines
Humans
Mice
SARS-CoV-2
Viral Vaccines
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Summary: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.
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ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.2200056