Obesity is associated with impaired immune history to influenza

Abstract Obesity is a risk factor of severe disease and mortality for both influenza and SARS-CoV-2. While previous studies show that obese individuals generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high compared to the healthy-weight group. To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the baseline immune history of obese and healthy-weight adults vaccinated with 2010–11 seasonal influenza vaccine to influenza antigens. Despite extensive heterogeneity in baseline immune history profiles in both groups, there were striking differences between obese and healthy controls, especially towards A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth towards a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933–2009, but increased IgG magnitude and breadth towards linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 baseline immune history, with young individuals with obesity more likely to have reduced A/H1N1 baseline immune history. We further found that IgG baseline immune history was associated with baseline and post-vaccination protective antibody responses, as measured by micro-neutralization and hemagglutinin inhibition assays. Taken together our findings suggest that increased susceptibility of obese subjects to influenza infection may be in-part mediated by obesity-associated differences in the memory antibody repertoire, which cannot be ameliorated by seasonal vaccination. Overall, these data have vital implications for the next generation of influenza and SARS-CoV-2 vaccines.