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Journal article
Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge
Frontiers in immunology, v 14
01 Mar 2023
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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- Title
- Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge
- Creators
- Ebony N. Gary - The Wistar InstituteNicholas J. Tursi - The Wistar InstituteBryce M. Warner - Public Health Agency of CanadaGina Cuismano - Drexel UniversityJennifer Connors - The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United StatesElizabeth M. Parzych - The Wistar InstituteBryan D. Griffin - Public Health Agency of CanadaMatthew R. Bell - Drexel University, Medicine (Graduate)Ali R. Ali - The Wistar InstituteDrew Frase - The Wistar InstituteCasey E. Hojecki - The Wistar InstituteGabriela A. Canziani - Drexel University, Biochemistry and Molecular BiologyIrwin Chaiken - Drexel UniversityToshitha Kannan - The Wistar InstituteEstella Moffat - Canadian Food Inspection AgencyCarissa Embury-Hyatt - Canadian Food Inspection AgencySarah K. Wooton - University of GuelphAndrew Kossenkov - The Wistar InstituteAmi Patel - The Wistar InstituteDarwyn Kobasa - Public Health Agency of CanadaMichele A. Kutzler - Drexel University, Infectious Diseases (and HIV Medicine)Elias K. Haddad - Drexel University, College of MedicineDavid B. Weiner - The Wistar Institute
- Publication Details
- Frontiers in immunology, v 14
- Publisher
- Frontiers Media S.A
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology; Medicine (Graduate); College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000956841300001
- Scopus ID
- 2-s2.0-85150885944
- Other Identifier
- 991020235077804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology