Vaccine induction of Salmonella-specific Th1 memory cells

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: STEPHEN J MCSORLEY
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2024
Award: $225,839
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY
A successful vaccine for systemic Salmonella infections will need to induce Th1 memory cells, but the tissue
location and required functionality of these cells is poorly understood. Our preliminary data show that liver
Tissue Resident Memory (TRM) CD4 T cells express higher levels of IL-18R and are more protective than the
corresponding TRMs cells in the lamina propria. In this application, we will test, (i) whether IL-18R expression
allows non-cognate responsiveness and robust TRM-mediated protection, and (ii) whether the use of a mRNA
nanoparticle delivery system can induce this protective population in the liver of vaccinated mice.

Terms: <0-11 years old><Abdominal Typhus><Activities of Daily Living><Activities of everyday life><Address><Adoptive Transfer><Age Months><Alleles><Allelomorphs><Anatomic Sites><Anatomic structures><Anatomy><Antigens><Antimicrobial Resistance><Blood><Blood Reticuloendothelial System><Body Tissues><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><Cause of Death><Cell Body><Cells><Cessation of life><Child><Child Youth><Children (0-21)><Class II Genes><Conjugate Vaccines><Data><Death><Development><Enteric Fever><Expression Signature><GWA study><GWAS><Gene Expression Profile><Goals><HLA Class II Genes><Hepatic Tissue><Heterogeneity><Immunity><Immunization><Infection><Intestinal><Intestines><Knowledge><Laboratories><Lamina Propria><Licensing><Life><Liver><Location><LoxP-flanked allele><Lymph><MHC Class II><MHC Class II Genes><Mediating><Memory><Messenger RNA><Mice><Mice Mammals><Murine><Mus><Phenotype><Population><Predisposition><RNA vaccine><RNA-based vaccine><Research Priority><Resistance><S enterica><S enterica serovar Typhi><S typhi><S typhosa><S. enterica><S. enterica serovar Typhi><S. typhi><S. typhosa><Salmonella><Salmonella enterica><Salmonella enterica serovar Typhi><Salmonella infections><Salmonella typhi><Salmonella typhosa><Salmonellosis><Subunit Vaccines><Susceptibility><System><Systemic disease><Systemic infection><T memory cell><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><Testing><Th-1 Cell><Th1 Cells><Tissue Model><Tissues><Type 1 Helper Cell><Typhoid><Typhoid Fever><Typhoid Vaccine><Vaccinated><Vaccination><Vaccines><Work><World Health Organization><access to vaccination><access to vaccines><anti-microbial resistant><bowel><daily living function><daily living functionality><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><effective therapy><effective treatment><experiment><experimental research><experimental study><experiments><floxed><floxed allele><functional ability><functional capacity><gene expression pattern><gene expression signature><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><hepatic body system><hepatic inflammation><hepatic organ system><immunogen><improved><inflamed liver><kids><liver inflammation><lymphatic fluid><mRNA><mRNA vaccine><mRNA-based vaccine><memory CD4 T cell><memory CD4 T lymphocyte><memory T lymphocyte><mouse model><murine model><nano particle delivery><nanoparticle delivered><nanoparticle delivery><new approaches><new vaccines><next generation vaccines><novel approaches><novel strategies><novel strategy><novel vaccines><pathogen><pre-clinical research><preclinical research><prevent><preventing><protective efficacy><residence><residential building><residential site><resistance to anti-microbial><resistant><resistant to antimicrobial><thymus derived lymphocyte><transcriptional profile><transcriptional signature><vaccination access><vaccination availability><vaccine access><vaccine availability><vaccine development><vaccine efficacy><whole genome association analysis><whole genome association studies><whole genome association study><youngster>