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. 2021 Jan 7;9(1):25.
doi: 10.3390/vaccines9010025.

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults

Chris P Verschoor  1   2 , Melissa K Andrew  3 , Mark Loeb  4 , Graham Pawelec  1   5 , Laura Haynes  6 , George A Kuchel  6 , Janet E McElhaney  1   2
Affiliations

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults

Chris P Verschoor et al. Vaccines (Basel). .

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.

Keywords: antibody; cell-mediated immunity; correlates of protection; influenza; older adults; vaccination.

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Conflict of interest statement

J.E.M. reports payments to her institution for her participation in advisory, scientific, or data safety and monitoring boards from Sanofi, G.S.K., Pfizer, Merck, ResTORbio, and Medicago, and as a site lead clinical trials sponsored by VBI and Jansen, outside the submitted work. L.H. reports payments from Spring Discovery for her work in an advisory capacity. M.L. reports grant funding, in-kind supply of vaccines, or honoraria for participation in advisory boards, from Seqirus, Sanofi, Medicago, and Pfizer. M.K.A. reports payments from GSK (grant funding), Sanofi (grants, honoraria and consulting fees) and Pfizer (grants and honoraria), outside the submitted work. G.A.K. reports grants from the US National Institutes of Health and honoraria for participation in advisory boards from ResTORbio, Janssen and Spring Discovery. C.P.V. and G.P. report no conflicts of interest. The funders had no role in the design of the study, collection, analyses, or interpretation of data, the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Change in antibody (HAI) titres and cell-mediated immune (CMI) measures over time depending on LCII-status at 10–20 weeks post-vaccination. Participants who developed (A) A/H3N2-LCII (n = 17) and (B) B-LCII (n = 9) are shown as blue, dashed lines, whereas participants who did not develop LCII (n = 582) are presented as red, solid lines. Measures at baseline (0) and 4-, 10- and 20-weeks post-vaccination are presented as the geometric mean and 95% confidence interval, of which, HAI titres are strain-specific, and CMI measures are in response to ex vivo challenge with either influenza A/H3N2 (A) or B (B). Note: IFNγ and IL-10 responses to B challenge were only measured in a subset of 80 non-LCII participants. Conc., concentration.
Figure 2
Figure 2
The association of participant demographics with the likelihood of laboratory-confirmed influenza illness (LCII). The odds ratio (OR) and 95% CI of LCII at 10–20 weeks post-vaccination are presented for age, sex, dose, site, CMV serostatus, BMI, and frailty. Estimates are relative to non-LCII participants (n = 582) and were derived separately for A/H3N2-LCII (n = 17; square points) and B-LCII (n = 9; round points) cases. Those estimates above the red dotted line (no difference) indicate a greater likelihood of LCII as compared to the reference group (i.e., second listed value), or per the relative unit as described in brackets. Note: since no B-LCII cases occurred at UCHC or in participants categorized as frail, estimates for site of frailty as a categorical variable could not be derived.
Figure 3
Figure 3
The association of antibody (HAI) titres and cell-mediated immune (CMI) measures with the likelihood of laboratory-confirmed influenza illness (LCII). The odds ratio (OR) and 95% CI of LCII at 10–20 weeks post-vaccination are presented. Estimates are relative to non-LCII participants (n = 582) and were derived for measures at baseline (0), 4-weeks, and the fold-change (FC) difference between the two time points, separately for (A) A/H3N2-LCII (n = 17) and (B) B-LCII (n = 9) cases. HAI titres are for A/H3N2 (A) and B (B) types, and CMI measures are in response to ex vivo challenge with either influenza A/H3N2 (A) or B (B). Those estimates above the red dotted line (no difference) indicate a greater likelihood of LCII for every 1-standard deviation change in the natural log-transformed measure.
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