Author:
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.
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.
Funder
National Institute of Allergy and Infectious Diseases
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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