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Co-immunization with adenosine deaminase rescues age-associated impairment of SARS-COV-2 synDNA vaccine-induced responses
Abstract   Peer reviewed

Co-immunization with adenosine deaminase rescues age-associated impairment of SARS-COV-2 synDNA vaccine-induced responses

Ebony Nicole Gary, Jennifer Connors, Nicholas J. Tursi, Bryce Warner, Matthew Bell, Gina Cuismano, Bhavani Taramangalam, Shiyu Zhang, Gabriela Canziani, Irwin C. Chaiken, …
The Journal of immunology (1950), v 206(1 Supplement), 30.03
01 May 2021
DOI: https://doi.org/10.4049/jimmunol.206.Supp.30.03

Abstract

SARS-CoV-2 is responsible for a global pandemic claiming over 2 million lives and infecting over 100 million people. Elderly patients display increased COVID-19 morbidity and mortality. Vaccine candidates have been studied and deployed in the clinic. However, age-associated immune deficits are known to cause sub-optimal responses, and the longevity of vaccine-induced responses is under investigation. Germinal center follicular helper T cells (TFH) promote affinity maturation of B cell receptors and memory B cell differentiation and are defined by expression of adenosine deaminase-1 (ADA-1). We investigated the adjuvant properties of plasmid-encoded adenosine deaminase (pADA) in the context of a SARS-CoV-2 spike synDNA antigens. Young and aged mice were immunized with plasmid-encoded spike (pS) alone or co-immunized with pS and pADA and cellular and humoral responses were evaluated. When immunized with pS alone, aged mice had decreased spike-binding IgG and neutralization titers. However, young and aged animals co-immunized with pADA had similar humoral responses. We observed similar trends in serum antibody affinity as measured by SPR. pADA co-immunization also rescued age-associated decreases in spike-specific IFNy secretion in the spleens and lungs of co-immunized aged mice as measured by ELISpot. Finally, preliminary data analysis indicates that co-immunization with pADA significantly impacts viral load in a model of SARS-CoV-2 infection. These data suggest that pADA enhances antigen-specific cellular and humoral immunity in aged mice and supports further study of this molecule as an immunoadjuvant for vaccines targeting elderly populations.

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