DYNAMIC cohort study evaluating metabolic predictors of influenza vaccine immune response in older adults

Abstract

Immunosenescence (age-related immune dysfunction) and inflamm-aging contribute to suboptimal immune responses in older adults to standard-dose influenza vaccines, which may be exacerbated in those with metabolic co-morbidities. We sought to investigate metabolic factors/predictors of influenza vaccine immune response in an older adult (age ≥65 years) cohort in Singapore, where influenza typically circulates year-round. The primary outcome for the DYNAMIC prospective cohort study was haemagglutination-inhibition titer (HAI) response to each of the trivalent inactivated influenza vaccine strains at day 28 (D28) compared to baseline (D0), as assessed by seroconversion and D28/D0 log2 HAI fold rise. Baseline blood samples were tested for total Vitamin D (25-(OH) D) levels. We enrolled 234 participants in June-Dec 2017. Two hundred twenty completed all study visits. The median age was 71 [IQR 68-75] years, 67 (30.5%) had diabetes mellitus (DM), and the median BMI was 24.9 [IQR 22.2-27.8] kg/m². Median baseline totals 25-(OH) D was 29 [IQR: 21-29] ng/ml. Age, DM, obesity, and baseline 25-(OH) D were not associated with HAI fold rise in multivariable analysis. More recent prior influenza vaccination and higher baseline HAI titers were associated with lower HAI fold rise for influenza A/HK/H3N2. Physical activity was associated with a higher HAI fold rise for influenza A/HK/H3N2 in a dose-response relationship (p-test for trend = 0.015). Older adults with well-controlled metabolic co-morbidities retain HAI response to the influenza vaccine, and physical activity had a beneficial effect on immune response, particularly for influenza A/HK/H3N2.

Fig. 1

Study participant flow diagram for the DYNAMIC cohort study showing the enrollment, follow-up and analysis phases.

Fig. 2. Geometric mean titers (GMT) pre-and post-influenza vaccine among full cohort for influenza A/HK/H3N2, A/MI/H1N1, and B-split, and among those with and without diabetes mellitus and obesity.

Panels a shows line graphs depicting GMT and 95% confidence intervals pre- and post-influenza vaccination for A/HK/H3N2, A/MI/H1N1 and B-split for the full cohort, subcategorized by their baseline seroprotection status (HAI of at least 1:40) for each respective strain. Panels b shows GMT and 95% confidence intervals pre- and post-influenza vaccination for the three strains amongst those with diabetes mellitus (n = 67) compared to those without. Panels c show GMT and 95% confidence intervals pre-and post-influenza vaccination for the three strains amongst those with obesity (n = 163, applying the same definition as in Tables 1 and 2) compared to those without. The embedded table displays the GMT and 95% CI data as shown in the corresponding panel line graphs.

Fig. 3. Outline of study visits, the DYNAMIC cohort study.

¶ anthropometric measurements comprised weight (kg), height (m), waist, and hip circumferences (cm). BMI (kg/m²), and waist: hip circumference ratios were calculated.