Increased dose of H1N1 pandemic influenza vaccine during pregnancy improves immunity in mothers and infants

Maternal-infant immunity against influenza is improved through vaccination during pregnancy. We conducted an in-depth analysis of antibody (Ab) responses in sera from pregnant and non-pregnant women immunized with an unadjuvanted inactivated influenza A (H1N1) monovalent vaccine during the 2009 pandemic ( NCT00992719 ). Pregnant women received either the standard 15µg- or increased 30µg-dose, while non-pregnant women received the 15µg-dose. Ab specific for influenza hemagglutinin (HA), HA stalk, and neuraminidase (NA), as well as canonical functions of hemagglutination inhibition (HAI), microneutralization, and neuraminidase inhibition were examined at baseline, 21 days post-vaccination, at delivery, and in cord blood. Ab subclasses, Fc receptor binding, and Fc-mediated immune functions, including cellular cytotoxicity, phagocytosis, and complement deposition, were also assessed. The vaccine was well-tolerated and highly immunogenic in recipients; most participants had a > 4-fold increase in Ab titers post-vaccination for HAI (HAI> 70%) and HA-specific IgG (IgG> 50%). Pregnant women who received the 15µg dose had a lower vaccine response in terms of NA-specific IgG and Fc receptor binding compared to the other groups. Immunization of pregnant women with the 30µg-dose resulted in more robust humoral immunity, including a larger number of HA Ab features reaching 4-fold increases compared to the other groups and a more durable antiviral function, and increased NA-specific Ab features that were transferred to the infant as compared to pregnant women who received the standard 15µg-dose. Increasing the antigen content in seasonal vaccines could be a means to enhance immunity against influenza in mothers and infants and deserves further study.