Profiling the Effect of Obesity on the Influenza Vaccine-Induced Antibody Repertoire Using Antigen Microarrays

Introduction: Influenza viruses cause up to 500,000 deaths per year worldwide. Vaccination is the most effective strategy for preventing influenza infection and is a key component for pandemic preparedness. However, vaccines fail to provide optimal protection in high-risk groups such as obese and the elderly. Obesity is a risk factor for developing severe influenza infection making vaccination of utmost importance for this high-risk population.

Methods: To study the effects of obesity on the anti-influenza antibody repertoire before and following influenza vaccination we used serum samples that were collected from healthy weight (Body Mass Index: 18.5≤BMI≤24.9) and obese (BMI > 30 kg/m2) patients at baseline and 30 days following vaccination with the 2010-2011 trivalent inactivated influenza vaccine (TIV). We developed a novel antigen microarray (AM), spotted with BPL-inactivated influenza A and B viruses, partially overlapping 20mer peptides of the hemagglutinin (HA) and neuraminidase (NA) surface proteins of the Cal2009 H1N1 vaccine strain (Cal09).

Results: We found that both healthy-weight and obese subjects generated antibodies against the vaccine strains as well as cross-reactive antibodies against other influenza viruses from the same subtypes. However, binding of serum antibodies to both peptides and whole virus antigens demonstrated significant differences between obese and healthy-weight humans. Healthy-weight subejcts generated stronger and broader antibody responses to the Cal09 vaccine strain, both pre- and post-vaccination. While both groups demonstrated a significant rise in the antibody titers to whole influenza viruses post-vaccination, this rise was higher and more significant in healthy-weight than in obese individuals.

Discussion: These findings suggest that healthy weight and obese individuals generate different repertoires of antibodies following TIV, and demonstrate that AMs can be used to identify population specific antibody responses that may be potential correlates of protection of influenza vaccines.