Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011-2012 influenza vaccine season

Background: We have previously reported an age-related impairment in the serum antibody response to pandemic (p) 2009 H1N1, measured by hemagglutination inhibition assay and ELISA. The present study extends these observations and evaluates IgG subclass distribution in healthy individuals of different ages vaccinated during the 2011-2012 season. Results: The 2011-2012 vaccination season was characterized by a vaccine containing the pandemic (p) 2009 H1N1 strain for the third consecutive year. All of our subjects were previously immunized, and therefore seroprotected at t0. Nevertheless, aging impaired the serum antibody response to H1N1, as antibody titers increased after vaccination in young and less in elderly individuals. The peak of the response was at day 7 (t7), in contrast with what is usually seen at day 21-28, suggesting a memory response characterized by the induction of an IgG subclass with a shorter half-life. We hypothesized that the IgG3 response, with its much shorter half-life, might be more represented. Antibodies were predominantly of the IgG1 subclass in both age groups, although a robust IgG3 response was also induced and accounted for a significant proportion of the overall response. IgG2 and IgG4 antibodies were at indiscernible levels. We showed a much higher percentage of IgG3 (40-50%) than previously in the literature (less than 10%). To explain if this was associated with a particular cytokine profile, we measured H1N1-induced T cell cytokines in vitro and found that IgG3 levels were positively correlated with TNF-alpha and IL-6. Moreover, activation-induced cytidine deaminase (AID) mRNA expression, a predictive biomarker of optimal in vivo vaccine response, was found to significantly correlate with IgG3 and also with IgG1 similar to what we have shown previously for total IgG. Conclusions: In the 2011-2012 season, the pandemic (p) 2009 H1N1 strain was present in the vaccine for the third consecutive year and therefore each individual was seroprotected at t0. The peak of the response was at t7, suggesting a memory response characterized by a robust induction of IgG3, which was associated with TNF-a and IL-6 production. Both IgG1 and IgG3 responses were decreased by age. AID was confirmed to be a predictive biomarker of optimal vaccine responses.