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