Clinical and immunologic predictors of influenza illness among vaccinated older adults

Abstract

The diagnosis of influenza is often missed in older adults and illness presentation may be modified by prior vaccination. We evaluated the symptoms and immunologic markers predicting laboratory-confirmed influenza (LCI) among vaccinated older adults. In subjects with influenza-like illness (ILI), fever distinguished subjects with laboratory-confirmed influenza (LCI) from those with other ILI (39% vs. 12.5%, p=0.009). In LCI subjects who did not seroconvert to influenza infection, pre-infection levels of the cytolytic mediator, granzyme B, correlated with fever (r=1.000; p=0.01) and the IFN-gamma:IL-10 ratio (r=0.999; p=0.03), and increased following influenza infection in LCI vs. ILI subjects (p=0.03). The cell-mediated immune response to influenza distinguishes A/H3N2 LCI from other ILI in older adults, and suggests a link between cell-mediated immunity and influenza illness severity in vaccinated older adults.

Figure 1

A flow chart of the results of influenza surveillance is shown for the two study sites (University of Connecticut Health Center [UCHC] and Vancouver). Laboratory confirmation for influenza A/H3N2 cases (Flu A) and influenza B (Flu B) are shown indicating the numbers of seroconverters (sero only), PCR-confirmed (swab only), or both, for subjects reporting influenza-like illness (ILI) symptoms.

Figure 2

PBMC stimulated 20 hours with live influenza virus and granzyme B (GzmB) activity measured in PBMC lysates stimulated with the A/H3N2 strain. Geometric mean GzmB levels represent combined data for the two study sites are shown for the pre- (0 wks) and post-vaccination (4- and 10-wks) time points in ILI subjects without laboratory confirmed A/H3N2 (No A/H3N2, n=77) and subjects who subsequently developed influenza after the 10-week time point (Flu A/H3N2, n=13). Error bars represent standard error of the mean.

Figure 3

Serum antibody titers to the three vaccine strains and IFN-γ and IL-10 levels in PBMC stimulated with A/H3N2 virus pre- (0 wks) and post-vaccination (4-, 10- and 20-wks) are shown for the Vancouver site. In subjects who developed influenza illness (between 10 and 20 weeks post-vaccination), subjects who were PCR+ only (PCR+, n=3) and those who seroconverted ± PCR+ (Sero, n=6) were compared to ILI subjects that did not develop influenza A/H3N2 (n=54). (A) serum antibody titers to the three vaccine strains, and (B) IFN-γ and IL-10 levels, and the IFN-γ:IL-10 ratio in A/H3N2-stimulated PBMC are shown. Error bars represent standard error of the mean.

Figure 4

Cytokine levels in PBMC stimulated with A/H3N2 virus pre- (0 wks) and post-vaccination (4-, 10- and 20-wks) are shown for the Vancouver site. In subjects who developed influenza illness, subjects who were PCR+ only (PCR+, n=3) and those who seroconverted ± PCR+ (Sero, n=6) were compared to subjects that did not develop influenza. Error bars represent standard error of the mean.