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Longevity and Determinants of Protective Humoral Immunity Following Pandemic Influenza Infection

tetano

Editor, Senior Moderator
Am J Respir Crit Care Med. 2014 Dec 15. [Epub ahead of print]
[h=1]Longevity and Determinants of Protective Humoral Immunity Following Pandemic Influenza Infection.[/h] Sridhar S[SUP]1[/SUP], Begom S, Hoschler K, Bermingham A, Adamson W, Carman W, Riley S, Lalvani A.
[h=3]Author information[/h]

[h=3]Abstract[/h] Rationale: Antibodies to influenza haemagglutinin (HA) are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity following primary influenza infection remain unclear. Objectives: The spread of a novel H1N1 (A(H1N1)pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity following a single primary influenza infection. Methods: We followed A(H1N1)pdm09 sero-negative adults through two influenza seasons (2009-2011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by haemagglutination-inhibition assay in individuals with paired serum samples collected pre- and post-infection or vaccination to assess durability of humoral immunity. Pre-existing A(H1N1)pdm09-specific multi-cytokine-secreting CD4 and CD8 T-cells were quantified by multi-parameter flow-cytometry to test the hypothesis that higher frequencies of CD4+ T-cell responses predict stronger antibody induction following infection or vaccination. Results: Antibodies induced by natural infection persisted at constant high titre for a minimum of ~15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titre following infection was inversely correlated to the frequency of pre-existing circulating A(H1N1)pdm09-specific CD4+IL-2+IFNg-TNF-α- T-cells (r=-0.4122,p=0.03). Conclusions: The longevity of protective humoral immunity following influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.


[h=4]KEYWORDS:[/h] Antibodies; Immunology; Pandemic influenza; T-cells; epidemiology

PMID: 25506631 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/25506631
 
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