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 15 µg dose or the increased 30 µg dose, while non-pregnant women received the 15 µg 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, was 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 15 µg dose had lower vaccine responses, as measured by NA-specific IgG, Fc receptor binding, and cell-mediated activity, compared with the other groups. Immunization of pregnant women with the 30 µg dose resulted in more robust humoral immunity, including a larger number of HA Ab features reaching 4-fold increases compared to the other groups, 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 15 µg dose. Increasing the antigen content of seasonal vaccines could enhance immunity against influenza in mothers and infants and warrants further study.IMPORTANCEPregnant women and infants are at-risk groups for influenza infection. Vaccination is recommended during pregnancy to stimulate adaptive immunity and protect both the mother and infant early in life. We characterized the immune responses of pregnant and non-pregnant women to an unadjuvanted inactivated 2009 pandemic influenza A (H1N1). Pregnant women immunized with the 15 µg standard seasonal influenza vaccine dose developed lower NA-specific responses compared to non-pregnant women immunized with the same vaccine dose. Vaccination of pregnant women with a 30 µg dose resulted in more robust and durable post-vaccination responses, particularly longer-lasting functional antibodies and NA-specific antibodies in maternal and cord blood. A deeper analysis of antibody responses beyond the traditional hemagglutination inhibition (HAI) assay suggests that a higher-dose influenza vaccine, already recommended for the elderly, could be beneficial for pregnant women and warrants further investigation.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT00992719.