Influenza A(H1N1)pdm09 But Not A(H3N2) Virus Infection Induces Durable Seroprotection: Results From the Ha Nam Cohort

Abstract

Background: The extent to which influenza recurrence depends upon waning immunity from prior infection is undefined. We used antibody titers of Ha-Nam cohort participants to estimate protection curves and decay trajectories.

Methods: Households (270) participated in influenza-like-illness (ILI) surveillance and provided blood at intervals spanning laboratory-confirmed virus transmission. Sera were tested in hemagglutination inhibition assay. Infection was defined as influenza virus-positive ILI and/or seroconversion. Median protective titers were estimated using scaled-logistic regression to model pretransmission titer against infection status in that season, limiting analysis to households with infection(s). Titers were modelled against month since infection using mixed-effects linear regression to estimate decay and when titers fell below protection thresholds.

Results: From December 2008-2012, 295 and 314 participants were infected with H1N1pdm09-like and A/Perth/16/09-like (H3N2Pe09) viruses, respectively. The proportion protected rose more steeply with titer for H1N1pdm09 than for H3N2Pe09, and estimated 50% protection titers were 19.6 and 37.3, respectively. Postinfection titers started higher against H3N2Pe09 but decayed more steeply than against H1N1pdm09. Seroprotection was estimated to be sustained against H1N1pdm09 but to wane by 8-months for H3N2Pe09.

Conclusions: Estimates indicate that infection induces durable seroprotection against H1N1pdm09 but not H3N2Pe09, which could in part account for the younger age of A(H1N1) versus A(H3N2) cases.

Keywords: H1N1 subtype; H3N2 subtype; antibody; cohort studies; immunity; influenza A virus.

Figure 1.

Study design. Diagrams depict protocols for selection and investigation of Ha Nam Cohort participants to detect H1N1pdm09 and H3N2Pe09 infections, and subsequently estimate HI titer protection thresholds, titer decay, and the duration seroprotection. Abbreviations: HI, hemagglutination inhibiting; ILI, influenza-like illness; RT-PCR, reverse transcription polymerase chain reaction.

Figure 2.

Age distribution of participants by infection status for each influenza A subtype from December 2008 to 2012. Dots represent individuals who were symptomatic and tested positive (ILI-PCR+), individuals without ILI symptoms but who seroconverted within a season (seroconverted), and individuals who neither seroconverted nor tested positive by PCR (uninfected). Violin plots show the distribution of individuals within age bands, while boxplots show the median and interquartile ranges. Mann-Whitney test P values compare participants with H1N1pdm09 versus H3N2Pe09 within each infection group. Abbreviations: ILI, influenza-like illness; PCR, polymerase chain reaction.

Figure 3.

Hemagglutination inhibiting (HI) protection curves. Estimated probability of protection according to preseason HI titer for H1N1pdm09 (left) and H3N2pe09 (right). Graphs show the median of the posterior distribution (solid line), and the 95% credible intervals (CI; grey shading). Dashed lines show the prior distribution. For H1N1pdm09 the median protective titer was estimated at 20 (95% CI, 2–40), while for H3N2pe09 the median protective titer was 37 (95% CI, 21–57).

Figure 4.

Estimated hemagglutination inhibiting (HI) antibody titer trajectories following H1N1pdm09 or H3N2Pe009 infection. A, The estimated decay modelled by subtype. B, Decay modelled by age group separately for H1N1pdm09 (left) and H3N2Pe09 (right). Dots indicate individual titers and are density-colored and jittered to permit visualization of the number of observations at each point. Lines show predicted mean titers and shaded areas show 95% prediction intervals. Dashed lines indicate the point at which the predicted means fell below the threshold for protection (a titer of 20 for H1N1pdm09 or 40 for H3N2Pe09).