Abstract
Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.
Highlights
Influenza remains an important public health concern, contributing significantly to mortality, morbidity and hospitalization rates worldwide, regardless of age or socioeconomic status [1]
The final sample of participants employed in our study was 608, 26 of whom developed laboratory-confirmed influenza illness (LCII) (A/H3N2, n = 17; B, n = 9); of these 26, 16 were confirmed by both serology and polymerase chain reaction (PCR) (A/H3N2, n = 8; B, n = 8), and the remaining by serology only (Table 1)
In another study when there was a good match to the circulating strain and influenza did not begin to circulate until after the 10-week post-vaccination time point, we found that a low IFNγ:IL-10 ratio at pre- and 4-weeks post-vaccination predicted increased risk for A/H3N2-LCII only in those who were PCR+ and had febrile LCII; importantly this group did not seroconvert to influenza infection [21]
Summary
Influenza remains an important public health concern, contributing significantly to mortality, morbidity and hospitalization rates worldwide, regardless of age or socioeconomic status [1]. Older adults are disproportionately burdened by influenza [1], and in general, vaccination provides much less protection than in younger age groups. 90% of influenza deaths and most influenza hospitalizations are in older adults, and this demographic is susceptible to severe outcomes of influenza A/H3N2 infection [2,3]. This is especially true when A/H3N2 is the predominant circulating strain, as hospitalization rates for adults 65 and older increase dramatically [4]. Efforts to improve influenza vaccine effectiveness in older adults have resulted in some success, such as the development of a high-dose seasonal trivalent split-virus influenza vaccine (HD-SVV), which is 24% more effective than standard dose formulation (SD-SVV) in preventing laboratoryconfirmed influenza illness (LCII) in adults 65 and over, largely against A/H3N2 LCII [5].
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