Journal article
Tissue resident memory T cells contribute to protectionagainst heterologousSARS-CoV-2 challenge
JCI insight, Vol.9(23), e184074
12/06/2024
DOI: 10.1172/jci.insight.184074
PMCID: PMC11623939
PMID: 39405115
Abstract
Widespread vaccination and natural infection have resulted in greatly decreased rates of severe disease, hospitalization and death after subsequent infection or reinfection with SARS-CoV-2. New vaccine formulations are based on circulating strains of virus, which have tended to evolve to more readily transmit human to human and to evade the neutralizing antibody response. An assumption of this approach is that ancestral strains of virus will not recur. Recurrence of these strains could be a problem for individuals not previously exposed to ancestral spike protein by vaccination or infection. Here, we addressed this question by infecting mice with recent SARS-CoV-2 variants and then challenging them with a highly pathogenic mouse-adapted virus closely related to the ancestral Wuhan-1 strain (SARS2-N501YMA30). We found that challenged mice were protected from death and substantial weight loss, even though they generally had low or no neutralizing antibody response to SARS2-N501YMA30 at the time of reinfection. T cell depletion from the previously infected mice did not diminish infection against clinical disease, although it did result in delayed kinetics of virus clearance in the nasal turbinate and in some cases, in the lungs. Levels of tissue resident memory T cells were significantly elevated in the nasal turbinate of previously infected mice compared to mice that had no previous exposure to SARS-CoV-2. However, this phenotype was not seen in lung tissues. Together, these results indicate that the immune response to newly circulating variants afforded protection against re-infection with the ancestral virus that was at least in part T cell based.
Details
- Title: Subtitle
- Tissue resident memory T cells contribute to protectionagainst heterologousSARS-CoV-2 challenge
- Creators
- Abby Odle - University of IowaMeenakshi Kar - Children's Healthcare of AtlantaAbhishek K Verma - University of IowaAlan Sariol - Washington University in St. LouisDavid K Meyerholz - University of IowaMehul S Suthar - Children's Healthcare of AtlantaLok-Yin Roy Wong - University of IowaStanley Perlman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.9(23), e184074
- DOI
- 10.1172/jci.insight.184074
- PMID
- 39405115
- PMCID
- PMC11623939
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Grant note
- National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services: 75N93021C00016, 75N93021C00017, 75N93021C00014 NIH: R01 AI129269, P51 OD011132, R00 AI170996
This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under contract no. 75N93021C00016, 75N93021C00017, and 75N93021C00014 and NIH grant R01 AI129269 (to SP) , P51 OD011132 (Emory Primate Center) and R00 AI170996 (to LYRW) . Schematics in Figures 1-4 were created using BioRender.com .
- Language
- English
- Electronic publication date
- 10/15/2024
- Date published
- 12/06/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984736600702771
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