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Abstract
Rationale: Antibodies to influenza hemagglutinin 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 after 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 after a single primary influenza infection.
Methods: We followed A(H1N1)pdm09-seronegative 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 hemagglutinationinhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific
multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD41 T-cell responses predict stronger antibody induction after infection or vaccination.
Measurements and Main Results: Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD41IL-21IFN-g2TNF-a2 T cells (r= 20.4122; P = 0.03).
Conclusions: The longevity of protective humoral immunity after 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.
Keywords: pandemic influenza; immunology; antibodies; T cells; epidemiology
Neutralizing antibodies against the surface glycoproteins, hemagglutinin and neuraminidase, of influenza virus are the primary mediators of protective immunity against influenza infection (1). Antigenic viral evolution and thereby global influenza circulation patterns are critically influenced by the nature of host humoral immunity. Recent work has shown that multiple influenza exposures, through infection or vaccination, can maintain antibody responses over a prolonged duration of time (2, 3). However, the durability of antibody responses after a single primary infection, as opposed to multiple infections, remains uncertain.
A previous study during the reemergence of 1977 H1N1 virus reported detectable levels of antibodies up to 3 years after infection in most children, although kinetics of antibody titer was not reported (4)....