Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection

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 CD4 1 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 CD4 1 IL-2 1 IFN-g 2 TNF-a 2 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.

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection

“…Several interventions in the 9-month period after influenza vaccination could have contributed to the loss of immune response including subsequent cycles of chemotherapy and/or corticosteroids. A recent study that prospectively measured HAI titers in adult persons at serial time points during the 2009 H1N1 pandemic showed that antibodies induced by natural infection maintained high titer for at least 15 months 39 . However, the titers significantly decreased at approximately 10 months compared to 3 months after vaccination 39 .…”

Immunity to Influenza. Preventing Infection and Regulating Disease

“…Acute disease was characterized by high levels Understanding the mechanisms underlying these correlates can lead to better diagnoses and interventions, including treatments and vaccines. Novel findings from this study (6) are indicated by bold text.…”

“…325-332) in this issue of the Journal (6). What are the natural mechanisms within the human host that allow for protection or permit pathology, and how can those be exploited to improve population outcomes to influenza?…”

“…Key correlates discovered in human populations during the course of naturally acquired influenza infection are outlined in Figure 1. The natural infection study design used in this study has many features that should be considered in future protocols and by large cohort initiatives, including the broad collection of baseline samples for longitudinal antibody titer comparison and its rapid establishment after the emergence of a new pandemic, allowing study of a single infection to reduce the effects of multiple influenza exposures (6). Future studies that incorporated this prospective design with longterm follow-up and included infants, hospitalized patients, and the elderly would be of great value to the clinical influenza community for designing new interventions for vaccination, diagnosis, and treatment.…”

Cytomegalovirus serostatus, inflammation, and antibody response to influenza vaccination in older adults: The moderating effect of beta blockade

“…However, these studies have not examined the effect of CMV serostatus on antibody persistence through the end of influenza season. Antibody persistence may contribute to clinical protection for over 6 months post-vaccination (Skowronski, Tweed,& De Serres, 2008), with one recent report suggesting protection through at least one subsequent influenza season (i.e., 1.5 years post-vaccination; Sridhar et al, 2015); thus, persistence is an equally important aspect of the antibody response to investigate. Peak antibody after vaccination depends mainly on short-lived plasma B cells, whereas antibody persistence depends on CD27+ memory B cells and long-lived plasma cells.…”