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

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

PROVIDER: PRJNA897899 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22179130.fastq.gz	Fastqsanger.gz
	SRR22179131.fastq.gz	Fastqsanger.gz
	SRR22179132.fastq.gz	Fastqsanger.gz
	SRR22179133.fastq.gz	Fastqsanger.gz
	SRR22179134.fastq.gz	Fastqsanger.gz

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

Project description:Aged patients suffer disproportionately increased morbidity and mortality associated with SARS-CoV-2 infection. Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, the aged patient population has suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterize vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in 18-month-old mice and interrogate protection. Aged mice have altered cellular responses, including decreased IFNγ secretion and increased TNFα secretion as compared to young mice. Aged mice had significantly decreased binding and neutralizing antibodies in their serum compared to their young counterparts. Co-immunization with the plasmid-encoded molecular adjuvant adenosine deaminase-1 (pADA) enhanced cellular responses and expanded the breadth of humoral responses in aged mice. pADA co-delivery also altered the gene expression profiles of lymph node lymphocytes in aged animals. Upon challenge pADA co-immunization modestly decreased age-associated morbidity and mortality in ACE2 transgenic and mouse-adapted SARS-CoV-2 challenge models. These data support the use of aged mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 and provide further support of the use of adenosine deaminase as a molecular adjuvant.

2023-02-28 | GSE217200 | GEO

New targets of Drosophila adenosine deaminase acting on RNA (dADAR)

Project description:The aim of this experiment is to identify new targets of Drosophila adenosine deaminase acting on RNA (dADAR) by enriching Inosine-containing mRNA (I-mRNA) from wild type (C-S) and dADAR mutant flies and then hybridization with Drosophila cDNA arrays.

2010-06-05 | E-GEOD-529 | biostudies-arrayexpress

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

Project description: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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Programmed RNA Editing with an Evolved Bacterial Adenosine Deaminase

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Programmed RNA Editing with an Evolved Bacterial Adenosine Deaminase II

Project description:Programmed RNA Editing with an Evolved Bacterial Adenosine Deaminase II

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Project description:Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells

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