Obesity is associated with impaired immune response to influenza vaccination in humans

Abstract

Background: Obesity is an independent risk factor for morbidity and mortality from pandemic influenza H1N1. Influenza is a significant public health threat, killing an estimated 250,000-500,000 people worldwide each year. More than one in ten of the world's adult population is obese and more than two-thirds of the US adult population is overweight or obese. No studies have compared humoral or cellular immune responses to influenza vaccination in healthy weight, overweight and obese populations despite clear public health importance.

Objective: The study employed a convenience sample to determine the antibody response to the 2009-2010 inactivated trivalent influenza vaccine (TIV) in healthy weight, overweight and obese participants at 1 and 12 months post vaccination. In addition, activation of CD8⁺ T cells and expression of interferon-γ and granzyme B were measured in influenza-stimulated peripheral blood mononuclear cell (PBMC) cultures.

Results: Body mass index (BMI) correlated positively with higher initial fold increase in IgG antibodies detected by enzyme-linked immunosorbent assay to TIV, confirmed by HAI antibody in a subset study. However, 12 months post vaccination, higher BMI was associated with a greater decline in influenza antibody titers. PBMCs challenged ex vivo with vaccine strain virus, demonstrated that obese individuals had decreased CD8⁺ T-cell activation and decreased expression of functional proteins compared with healthy weight individuals.

Conclusion: These results suggest obesity may impair the ability to mount a protective immune response to influenza virus.

Figure 1

Obese participants do not have an impaired initial response to influenza vaccination. Boxplots of the fold increase of the geometric mean titers of HAI response for each vaccine strain. Wilcoxon signed rank test of fold increase of healthy weight vs obese: (a) A/Brisbane/59/2007, P=0.14; (b) A/Brisbane 10/2007, P=0.09; (c) B/Brisbane/60/2008, P=0.04. Healthy weight n=40, obese n=40.

Figure 2

Obesity results in a greater decline of influenza antibodies. (a) Correlation between BMI and percent antibody drop of ELISA titers. As the BMI increases, the drop in antibody at 12 months postvaccination is increased. Spearman's rank correlation: r=0.29 (P=0.01), n=74. (b) More obese individuals have a >4-fold drop in HAI titer at 12 months post vaccination compared with healthy weight individuals (McNemar's test P=0.16 for A/Brisbane/59, P=0.32 for A/Brisbane/10 and P=0.03 for B/Brisbane/60). Healthy weight n=17, obese n=17.

Figure 3

Obesity results in defective CD8⁺ T-cell activation and production of the functional proteins Granzyme B and IFNγ by influenza-stimulated PBMCs. (a) PBMCs from obese participants have a lower-percent increase in activated CD69-expressing CD8⁺ T cells (P=0.015) and (b) a lower-pecentage increase in activated T cells that express Granzyme B (P=0.026) compared with healthy weight. (c) PBMCs from overweight and obese participants have a lower-percent increase in activated CD8⁺ T cells that express IFNγ (P=0.047 and P=0.006, respectively). The percent increase in cell number for each population of cells was calculated between PBMCs incubated with plain media and PBMCs incubated with influenza A virus. As such, each individual sample was compared with its own control. Bar graphs show mean percent increase and standard error for the three groups. Healthy weight n=23, overweight n=17, obese n=21. ^*indicates P-value is <0.05 compared with the healthy weight group. GrB=Granzyme B.