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Determining Adenosine Deaminase 1 (ADA-1) Impact on Immune Memory and Durability as a Molecular Adjuvant in a SARS-CoV-2 DNA Vaccine Formulation
Journal article   Peer reviewed

Determining Adenosine Deaminase 1 (ADA-1) Impact on Immune Memory and Durability as a Molecular Adjuvant in a SARS-CoV-2 DNA Vaccine Formulation

Gina Cusimano, Ebony N. Gary, Matt Bell, Jennifer R Connors, Nicholas J. Tursi, Shiyu Zhang, Gabriela Canziani, Bryce Warner, Ali R. Ali, Bhavani Taramangalam, …
The Journal of immunology (1950), v 206(1_Supplement), pp 30-30.04
01 May 2021
DOI: https://doi.org/10.4049/jimmunol.206.Supp.30.04

Abstract

Abstract The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease of 2019 (COVID-19), has infected millions of people causing a global pandemic. SARS-CoV-2 vaccines candidates have demonstrated acute immunogenicity and protection however, it has yet to be demonstrated whether natural or vaccine induced immunity against SARS-CoV-2 induces long term, protective immunity. In this study we sought to understand if adenosine deaminase (ADA), as a molecular adjuvant, can enhance immune memory and durability in the context of a SARS-CoV-2 DNA vaccine. Mice were immunized with a plasmid encoding for SARS-CoV-2 spike alone or in combination with plasmid encoded ADA. Subsequent B and T cell responses were measured until d60pi. In mice co-immunized with ADA, there were increased concentrations of spike receptor binding domain (RBD)-specific IgG in the sera which were found to bind RBD at an increased affinity as well as exhibit increased neutralization capability against SARS-CoV-2 pseudotyped viruses. Additionally, ADA co-immunized mice exhibited increased frequency of RBD specific memory B cells. In regard to T cell responses, mice co-immunized with ADA exhibited increased spike-specific IFN-γ, TNF-a and IL-2 as measured by flow cytometry and ELISpot. The ADA-enhanced anti-spike antibody durability over time was associated with increased frequencies of T follicular helper cells (TFH). Preliminary analysis supports that co-immunization with pADA impacts viral load in a SARS-CoV-2 infection model. These data suggest that ADA enhances immune memory and durability and supports further study with translational focus for enhancement of vaccines.

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