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

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.30-30.04
• Main Authors: Cusimano, Gina, Gary, Ebony N., Bell, Matt, Connors, Jennifer R, Tursi, Nicholas J., Zhang, Shiyu, Canziani, Gabriela, Warner, Bryce, Ali, Ali R., Taramangalam, Bhavani, Chaiken, Irwin C., Wootton, Sarah, Weiner, David, Kobasa, Darwyn, Kutzler, Michele A., Haddad, Elias K.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.206.Supp.30.04

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.