Giuseppe
Emeritus
[Source: Nature Medicine, full page: (LINK). Abstract, edited.]
Nature Medicine | Article
Cellular immune correlates of protection against symptomatic pandemic influenza
Saranya Sridhar,<SUP>1 </SUP>Shaima Begom,<SUP>1 </SUP>Alison Bermingham,<SUP>2 </SUP>Katja Hoschler,<SUP>2 </SUP>Walt Adamson,<SUP>3 </SUP>William Carman,<SUP>4 </SUP>Thomas Bean,<SUP>5 </SUP>Wendy Barclay,<SUP>6 </SUP>Jonathan J Deeks<SUP>7 </SUP>& Ajit Lalvani<SUP>1</SUP>
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Journal name: Nature Medicine - Year published: (2013) - DOI: doi:10.1038/nm.3350
Received 04 June 2013 ? Accepted 19 August 2013 - Published online 22 September 2013
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)<SUP>+</SUP> interleukin-2 (IL-2)<SUP>−</SUP> CD8<SUP>+</SUP> T cells (r = −0.6, P = 0.004). Within this functional CD8<SUP>+</SUP>IFN-γ<SUP>+</SUP>IL-2<SUP>−</SUP> population, cells with the CD45RA<SUP>+</SUP> chemokine (C-C) receptor 7 (CCR7)<SUP>−</SUP> phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8<SUP>+</SUP> 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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Author information: 1 Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK. 2 Respiratory Virus Unit, Centre for Infections, Public Health England, London, UK. 3 West of Scotland Specialist Virology Centre, Glasgow, UK. 4 Centre for Virus Research, University of Glasgow, Glasgow, UK. 5 Public Health England Microbiology Services, Porton Down, UK. 6 Department of Virology, National Heart and Lung Institute, Imperial College London, London, UK. 7 Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
Contributions: A.L. conceived the study, and S.S. and A.L. designed the study. S.S. coordinated the study. S.S., S.B., T.B., W.C., W.A., A.B. and K.H. performed the laboratory assays. S.S., A.L. and J.J.D. analyzed and interpreted the data. S.S., S.B. and A.L. drafted the article with critical revisions and important intellectual content provided by J.J.D., K.H. and W.B.
Competing financial interests: S.S., A.L. and S.B. are named inventors on a patent application relating to the design and evaluation of influenza vaccines and the risk stratification of influenza illness.
Corresponding author: Ajit Lalvani
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Nature Medicine | Article
Cellular immune correlates of protection against symptomatic pandemic influenza
Saranya Sridhar,<SUP>1 </SUP>Shaima Begom,<SUP>1 </SUP>Alison Bermingham,<SUP>2 </SUP>Katja Hoschler,<SUP>2 </SUP>Walt Adamson,<SUP>3 </SUP>William Carman,<SUP>4 </SUP>Thomas Bean,<SUP>5 </SUP>Wendy Barclay,<SUP>6 </SUP>Jonathan J Deeks<SUP>7 </SUP>& Ajit Lalvani<SUP>1</SUP>
<SUP></SUP>
<SUP></SUP>
Journal name: Nature Medicine - Year published: (2013) - DOI: doi:10.1038/nm.3350
Received 04 June 2013 ? Accepted 19 August 2013 - Published online 22 September 2013
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)<SUP>+</SUP> interleukin-2 (IL-2)<SUP>−</SUP> CD8<SUP>+</SUP> T cells (r = −0.6, P = 0.004). Within this functional CD8<SUP>+</SUP>IFN-γ<SUP>+</SUP>IL-2<SUP>−</SUP> population, cells with the CD45RA<SUP>+</SUP> chemokine (C-C) receptor 7 (CCR7)<SUP>−</SUP> phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8<SUP>+</SUP> 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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Author information: 1 Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London, UK. 2 Respiratory Virus Unit, Centre for Infections, Public Health England, London, UK. 3 West of Scotland Specialist Virology Centre, Glasgow, UK. 4 Centre for Virus Research, University of Glasgow, Glasgow, UK. 5 Public Health England Microbiology Services, Porton Down, UK. 6 Department of Virology, National Heart and Lung Institute, Imperial College London, London, UK. 7 Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
Contributions: A.L. conceived the study, and S.S. and A.L. designed the study. S.S. coordinated the study. S.S., S.B., T.B., W.C., W.A., A.B. and K.H. performed the laboratory assays. S.S., A.L. and J.J.D. analyzed and interpreted the data. S.S., S.B. and A.L. drafted the article with critical revisions and important intellectual content provided by J.J.D., K.H. and W.B.
Competing financial interests: S.S., A.L. and S.B. are named inventors on a patent application relating to the design and evaluation of influenza vaccines and the risk stratification of influenza illness.
Corresponding author: Ajit Lalvani
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