Cellular immune correlates of protection against symptomatic pandemic influenza

Research output: Contribution to journalArticle

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Cellular immune correlates of protection against symptomatic pandemic influenza. / Sridhar, Saranya; Begom, Shaima; Bermingham, Alison; Hoschler, Katja; Adamson, Walt; Carman, William; Bean, Thomas; Barclay, Wendy; Deeks, Jonathan J; Lalvani, Ajit.

In: Nature Medicine, Vol. 19, No. 10, 10.2013, p. 1305-12.

Research output: Contribution to journalArticle

Harvard

Sridhar, S, Begom, S, Bermingham, A, Hoschler, K, Adamson, W, Carman, W, Bean, T, Barclay, W, Deeks, JJ & Lalvani, A 2013, 'Cellular immune correlates of protection against symptomatic pandemic influenza', Nature Medicine, vol. 19, no. 10, pp. 1305-12. https://doi.org/10.1038/nm.3350

APA

Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., Bean, T., Barclay, W., Deeks, J. J., & Lalvani, A. (2013). Cellular immune correlates of protection against symptomatic pandemic influenza. Nature Medicine, 19(10), 1305-12. https://doi.org/10.1038/nm.3350

Vancouver

Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nature Medicine. 2013 Oct;19(10):1305-12. https://doi.org/10.1038/nm.3350

Author

Sridhar, Saranya ; Begom, Shaima ; Bermingham, Alison ; Hoschler, Katja ; Adamson, Walt ; Carman, William ; Bean, Thomas ; Barclay, Wendy ; Deeks, Jonathan J ; Lalvani, Ajit. / Cellular immune correlates of protection against symptomatic pandemic influenza. In: Nature Medicine. 2013 ; Vol. 19, No. 10. pp. 1305-12.

Bibtex

@article{04e1e919578b474c828dc648bc980160,
title = "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.",
keywords = "Adult, CD8-Positive T-Lymphocytes, Cohort Studies, Cross Reactions, Great Britain, Humans, Immunity, Cellular, Immunologic Memory, Immunophenotyping, Influenza A Virus, H1N1 Subtype, Influenza, Human, Severity of Illness Index, Virus Shedding",
author = "Saranya Sridhar and Shaima Begom and Alison Bermingham and Katja Hoschler and Walt Adamson and William Carman and Thomas Bean and Wendy Barclay and Deeks, {Jonathan J} and Ajit Lalvani",
year = "2013",
month = oct,
doi = "10.1038/nm.3350",
language = "English",
volume = "19",
pages = "1305--12",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Cellular immune correlates of protection against symptomatic pandemic influenza

AU - Sridhar, Saranya

AU - Begom, Shaima

AU - Bermingham, Alison

AU - Hoschler, Katja

AU - Adamson, Walt

AU - Carman, William

AU - Bean, Thomas

AU - Barclay, Wendy

AU - Deeks, Jonathan J

AU - Lalvani, Ajit

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Adult

KW - CD8-Positive T-Lymphocytes

KW - Cohort Studies

KW - Cross Reactions

KW - Great Britain

KW - Humans

KW - Immunity, Cellular

KW - Immunologic Memory

KW - Immunophenotyping

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza, Human

KW - Severity of Illness Index

KW - Virus Shedding

U2 - 10.1038/nm.3350

DO - 10.1038/nm.3350

M3 - Article

C2 - 24056771

VL - 19

SP - 1305

EP - 1312

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 10

ER -