Effects of Obesity on the Influenza Immune-History and Responses to Influenza Vaccination

Marwa Abd Alhadi ^1,2 Lilach M. Friedman ^1,2 Liel Cohen ^1,2 Erik Karlsson ³ Melinda Beck ⁴ Tomer Hertz ^1,2,5

¹The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel, Israel
²National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel, Israel
³Virology Institut, virology Institut Pasteur Du Cambodge, Phnom Penh, Cambodia;, Cambodia
⁴Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, Nc, Usa, USA
⁵Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Wa, Usa., USA

Influenza viruses cause up to 500,000 deaths annually, and seasonal vaccination significantly reduces the risk of infection. While obese subjects generate a significant vaccine-induced rise in antibody titers following vaccination, the infection rate in this group was double as compared to healthy weight subjects.

To study the effect of obesity on the anti-influenza antibody repertoire we used serum samples from healthy-weight (HW, n=112, 24.9≥BMI≥18.5) and obese (n=108, BMI≥ 30) subjects at baseline and 30 days post-vaccination with the seasonal influenza vaccine. We developed a novel antigen microarray spotted with BPL-inactivated influenza viruses, recombinant hemagglutinin (HA) proteins and partially overlapping 20mer peptides of the HA and NA proteins of the vaccine strain.

We found that while both HW and obese subjects generated similar rises in IgG antibody titers post-vaccination, HW subjects had higher baseline IgG titers to influenza strains. In contrast, baseline IgA titers were overall similar, and a significant rise was detected in obese subjects. Ranking subjects by their baseline immune-history magnitude to H1N1 strains was associated with obesity and BMI: individuals with low magnitudes were more likely to be obese than those with high-magnitudes (p=0.003) and were also younger on average (p=0.00005). Importantly, there was no association between BMI and age. A prediction model for obesity trained on peptide antibody profiles was able to obtain an AUC score of 0.88.

These findings suggest that the increased susceptibility of obese subjects to influenza may be related to differences in the baseline antibody repertoire, as well as in the vaccine-induced responses.