Cellular immune correlates of protection against symptomatic pandemic influenza
Abstract
The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Higher frequencies of pre-existing T cells to conserved CD8 epitopes were found in individuals who developed less severe illness, with total symptom score having the strongest inverse correlation with the frequency of interferon-γ (IFN-γ)(+) interleukin-2 (IL-2)(-) CD8(+) T cells (r = -0.6, P = 0.004). Within this functional CD8(+)IFN-γ(+)IL-2(-) population, cells with the CD45RA(+) chemokine (C-C) receptor 7 (CCR7)(-) phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8(+) T cells specific to conserved viral epitopes correlated with crossprotection against symptomatic influenza. This protective immune correlate could guide universal influenza vaccine development.
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Cross-reactive T cells can provide some degree of protective immunity against respiratory viral infections, as seen in the 2009 influenza H1N1 pandemic.
“Cross-reactive T cells can provide some degree of protective immunity against respiratory viral infections, as seen in the influenza H1N1 2009 pandemic (Sridhar et al., 2013; Wilkinson et al., 2012).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Sridhar et al., 2013
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- Authors
- Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., Bean, T., Barclay, W., Deeks, J. J., & Lalvani, A.
- Affiliations
- Imperial College London (GB)
- Public Health England (GB)
- MRC University of Glasgow Centre for Virus Research (GB)
- University of Birmingham (GB)
- Corresponding author
- Lalvani, Ajit
- Venue
- Nature Medicine
- Published
- 2013-09-22
- Volume
- 19
- Issue
- 10
- Pages
- 1305-1312
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2076787697
- Cited by
- 862
- References
- 58
- Citations by year
- 2026: 37 · 2025: 47 · 2024: 60 · 2023: 63 · 2022: 69 · 2021: 94 · 2020: 85 · 2019: 74 · 2018: 83 · 2017: 53 · 2016: 68 · 2015: 76 · 2014: 44 · 2013: 6 · 2012: 1
- FWCI
- 47.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Harvard University
- Wellcome Trust
- Imperial College London
- University of Oxford
- Medical Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- 2009 H1N1 pandemic, correlates of protection, CD8+ T cells, disease severity, interferon-gamma, interleukin-2, CCR7, CD45RA, cytotoxic T lymphocytes, universal influenza vaccine, heterosubtypic immunity
- MeSH terms
- Adult, Cross Reactions, United Kingdom, Humans, Immunity, Cellular, Immunologic Memory, Influenza, Human, Severity of Illness Index, Cohort Studies, Immunophenotyping, Virus Shedding, CD8-Positive T-Lymphocytes, Influenza A Virus, H1N1 Subtype
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