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

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Abstract 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. Importance Pregnant 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 15µg 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 an increased 30µg dose resulted in more robust and durable responses post-vaccination, 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), suggests that a higher-dose influenza vaccine, already recommended for the elderly, could be beneficial for pregnant women and is worth exploring.

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