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

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DOI

https://doi.org/10.3389/fimmu.2023.1138609

Language of the publication
English
Date
2023-03-14
Type
Article
Author(s)
  • Gary, Ebony N.
  • Tursi, Nicholas J.
  • Warner, Bryce M.
  • Cuismano, Gina
  • Connors, Jennifer
  • Parzych, Elizabeth M.
  • Griffin, Bryan D.
  • Bell, Matthew R.
  • Ali, Ali R.
  • Frase, Drew
  • Hojecki, Casey E.
  • Canziani, Gabriela A.
  • Chaiken, Irwin
  • Kannan, Toshitha
  • Moffat, Estella
  • Embury-Hyatt, Carissa
  • Wooton, Sarah K.
  • Kossenkov, Andrew
  • Patel, Ami
  • Kobasa, Darwyn
  • Kutzler, Michele A.
  • Haddad, Elias K.
  • Weiner, David B.
Publisher
Frontiers Media S.A.

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.

Subject

  • Health,
  • Science and technology

Rights

Peer review

Yes

Open access level

Gold

Identifiers

ISSN
1664-3224

Article

Journal title
Frontiers in Immunology
Journal volume
14
Accepted date
2023-02-23
Submitted date
2023-01-05

Citation(s)

Gary, E. N., Tursi, N. J., Warner, B. M., Cuismano, G., Connors, J., Parzych, E. M., Griffin, B. D., Bell, M. R., Ali, A. R., Frase, D., Hojecki, C. E., Canziani, G. A., Chaiken, I., Kannan, T., Moffat, E., Embury-Hyatt, C., Wooton, S. K., Kossenkov, A., Patel, A., … Weiner, D. B. (2023). Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and Challenge. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1138609

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