Influenza A virus-specific maternal antibodies impair vaccine-induced antibody responses and protection in male to a greater extent than female offspring.

Abstract

Abstract Influenza A virus (IAV) is a public health threat to pregnant people and infants. Transfer of antibodies across the placenta to the fetus and during lactation provides key protection from infectious pathogens during the neonatal period. Despite this, pathogen-specific maternal antibodies may interfere with infant vaccination. We hypothesized that transfer of IAV-specific maternal antibody, would negatively affect vaccine-induced immunity and protection in male and female offspring, with males being more impacted. Pregnant CD1 mice were infected on embryonic day 10 with 103TCID50 of mouse adapted A/California/09 H1N1 (ma2009 H1N1) or mock inoculated. In offspring of IAV-infected dams, maternal anti-ma2009 H1N1 IgG peaked at 3-weeks, declined at 7-weeks, and undetectable at 15-weeks of age. At 3-, 7-, and 15-weeks, male and female offspring were intramuscularly vaccinated with inactivated ma2009 H1N1 vaccine, boosted 21 days later, and had serum collected 14 days post-boost. Following vaccination, 3-week-old offspring of IAV-infected dams displayed significantly lower vaccine-induced anti-ma2009 H1N1 IgG titers compared to offspring born from mock-infected dams. At 7 weeks of age, vaccine-induced IgG titers were significantly inhibited in male but not female offspring. In 15-week-old offspring of IAV-infected dams, vaccine-induced antibody responses were similar to offspring of mock-infected dams, being greater in female than male offspring. These data suggest that IAV-specific maternal antibodies negatively impact the offspring response to IAV-vaccination, with this more pronounced in males than females. This research is important for understanding the factors that impact vaccine-induced immunity in early life. Supported by funding from the Johns Hopkins Vivien Thomas Scholars Initiative and grants from NIH/NICHD R01 HD097608, JH-CEIRS contract HHSN272201400007C, and NIH/NIA U54AG062333, NIH/NIAD 2T32A1007417-26