Influenza vaccination during early pregnancy contributes to neurogenesis and behavioral function in offspring

Prenatal influenza virus infection has been associated with an increased risk of schizophrenia. Thus, inactivated flu vaccines are widely recommended for pregnant women. In a mouse model of pregnancy, immune activation via exposure to viruses or lipopolysaccharide (LPS) impaired brain development and behavioral function in offspring. The objective of our study was to determine if flu vaccination as an immune activation could affect postnatal neurogenesis and behavior. Female C57BL/6J mice were administered A(H1N1) influenza vaccine (AIV) or seasonal influenza vaccine (SIV) early in pregnancy. We found that the offspring of vaccinated mice, especially AIV group, presented superior performance in terms of exploratory behavior and spatial ability compared with controls at postnatal day 28 (P28), but at P56, there was no significance differences among these pups. Quantification of BrdU(+)/DCX(+) and BrdU(+)/NeuN(+) cells in the dentate gyrus (DG) indicated an increase in the hippocampal neurogenesis of the pups born to both vaccinated mothers. The cytokine levels in both the serum and hippocampus changed to varying degrees. Furthermore, administration of the A(H1N1) vaccine blocked LPS-induced cognitive impairment in the progeny. Altogether, the results suggest that maternal influenza vaccination promotes neurogenesis and behavioral function, as well as protection from LPS insults in the developing offspring.