Maternal immunization against enteric pathogens is protective in a model of late-onset sepsis 2963

Abstract Description Infants are vulnerable to infectious diseases due to the immaturity of their immune system, including a delay in producing pathogen-targeting antibodies. Maternal immunization strategies have increased in use to protect infants from disease by vertical transfer of protective pathogen-specific antibodies. Late-onset sepsis (LOS) is a substantial contributor to neonatal mortality that results from a bloodstream infection at least 72 hours after birth. The implicated pathogen is often a member of the intestinal microbiome before systemic infection, suggesting translocation from the intestine as the path to the bloodstream. We hypothesized that maternal immunization of animals prior to pregnancy could protect nursing pups in a murine model of LOS. Following maternal immunization against Enterobacteriaceae taxa implicated in sepsis, we observed significantly decreased pup mortality following an oral challenge with Escherichia coli. This protection was associated with increases in antigen-specific IgG and IgA in both the mammary tissue of vaccinated dams and stomach contents of nursing pups. Interestingly, we did not observe differences in the infant microbiota following maternal vaccination, suggesting increased pathogen-specific IgG and IgA did not perturb the developing microbiota. This work suggests maternal immunization may be useful to protect offspring from enteric pathogens, and further supports the role of human milk and human milk factors in protection from LOS. Funding Sources Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) Topic Categories Vaccines and Immunotherapy (VAC)