LAIV vaccination prior to pregnancy protects against lethal influenza infection and prevents infection-associated outcomes in offspring

Abstract

Abstract Influenza is a highly contagious respiratory infection of public health concern. Pregnant women are among those at greater risk of suffering from serious influenza A virus (IAV) infection. Compromised cell-mediated immune responses, low inactivated vaccine efficacy, and poor vaccine uptake all increase the likelihood that exposure to the virus during pregnancy will result in infection-associated maternal and gestational complications such as stillbirths, preterm delivery, and low birthweights. The protective potential of IAV-specific immunological T cell memory induced by vaccination with a cold adapted live attenuated influenza vaccine (LAIV) during pregnancy has not been described; this immunity has the potential to mediate universal protection against influenza. Here, we investigated how LAIV priming before pregnancy and subsequent heterosubtypic IAV challenge during pregnancy impacts maternal and fetal outcomes in mice. LAIV priming prior to pregnancy completely protects pregnant dams against the morbidity and mortality of infection that is lethal to unprimed mice and primed dams go on to drop average sized litters. Pups born to unprimed dams are significantly smaller in terms of weight on days 3, 7, 14, and 21 when compared to pups born to LAIV primed dams. In contrast, morphological development determined by crown-rump length and skeletal measurements, while initially hindered, does not significantly differ between pups born to unprimed and primed dams after the first week following birth. LAIV priming prior to pregnancy thus appears to prevent adverse maternal and fetal IAV-associated outcomes. These data support that LAIV has potential for use as a universal vaccine to protect pregnant females against pandemic IAV.