The role of influenza hemagglutination-inhibition antibody as a vaccine mediator in children

Abstract

Background. Vaccination may protect through the humoral immune response, or cellular immune response, or most likely both. The humoral pathway can be mediated through the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (called direct effect) for different influenza types and subtypes. Methods. We analysed data from a cluster randomized trial where Canadian Hutterite children were vaccinated and assessed the 2008-2009 season to estimate the effect of higher HAI titer in protection against influenza. We included data from 618 children from 46 colonies, aged between 3 and 15 years with a mean age of 9.06 years who were vaccinated with inactivated trivalent influenza vaccine or hepatitis A vaccine. We used the inverse odds ratio weighting method to calculate the direct and indirect effect of vaccination against influenza A/H3N2 and influenza B/Brisbane by regressing vaccination on HAI titer. Results. Our results show that the vaccine efficacy was 63% for influenza A (H3N2) and 28% for influenza B. The hazard ratio for the direct and indirect effect of vaccination for protection against influenza A/H3N2 was 0.38 (95% confidence interval [CI] of 0.00 to 5.47) and 0.96 (95%CI of 0.00 to 2.89) respectively. The hazard ratio for influenza B direct and indirect effect was 0.96 (95% CI of 0.00 to 12.02) and 0.75 (95%CI of 0.07 to 1) respectively. Conclusions. Although vaccination provided a higher protective effectiveness against influenza A in children, only 3.82% of this protection was mediated through the indirect pathway, that is through rise of hemagglutination inhibition titer. In contrast, more than 85% of the protection against influenza B occurred through rise of HAI titer.