Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge.

Abstract

Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice. Aged mice exhibited altered cellular responses, including decreased IFNγ secretion and increased TNFα and IL-4 secretion suggestive of TH2-skewed responses. Aged mice exhibited decreased total binding and neutralizing antibodies in their serum but significantly increased TH2-type antigen-specific IgG1 antibody compared to their young counterparts. Strategies to enhance vaccine-induced immune responses are important, especially in aged patient populations. We observed that co-immunization with plasmid-encoded adenosine deaminase (pADA)enhanced immune responses in young animals. Ageing is associated with decreases in ADA function and expression. Here, we report that co-immunization with pADA enhanced IFNγ secretion while decreasing TNFα and IL-4 secretion. pADA expanded the breadth and affinity SARS-CoV-2 spike-specific antibodies while supporting TH1-type humoral responses in aged mice. scRNAseq analysis of aged lymph nodes revealed that pADA co-immunization supported a TH1 gene profile and decreased FoxP3 gene expression. Upon challenge, pADA co-immunization decreased viral loads in aged mice. These data support the use of mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 vaccines and provide support for the use of adenosine deaminase as a molecular adjuvant in immune-challenged populations.

• Authors: Ebony N Gary, Nicholas J Tursi, Bryce M Warner, Gina Cuismano, Jennifer Connors, Elizabeth M Parzych, Bryan D Griffin, Matthew R Bell, Ali R Ali, Drew Frase, Casey E Hojecki, Gabriela A Canziani, Irwin Chaiken, Toshitha Kannan, Estella Moffat, Carissa Embury-Hyatt, Sarah K Wooton, Andrew Kossenkov, Ami Patel, Darwyn Kobasa, Michele A Kutzler, Elias K Haddad, David B Weiner
• Journal: Frontiers in immunology (Front Immunol) Vol. 14 Pg. 1138609 ( 2023) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 36999023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2023 Gary, Tursi, Warner, Cuismano, Connors, Parzych, Griffin, Bell, Ali, Frase, Hojecki, Canziani, Chaiken, Kannan, Moffat, Embury-Hyatt, Wooton, Kossenkov, Patel, Kobasa, Kutzler, Haddad and Weiner.

Chemical References

• COVID-19 Vaccines
• Tumor Necrosis Factor-alpha
• Interleukin-4
• Adenosine Deaminase
• Antibodies, Viral

Topics

• Humans
• Animals
• Mice
• SARS-CoV-2
• COVID-19 Vaccines
• Tumor Necrosis Factor-alpha
• COVID-19
• Interleukin-4
• Adenosine Deaminase
• Immunization
• Antibodies, Viral
• Disease Models, Animal