Infant Immunity

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PROJECT 3 – ABSTRACT Antibodies transferred from the mother to the fetus are a central determinant of immunity during the first months of life. They provide protection against infectious pathogens when the magnitude and avidity of infant antibody responses are relatively low. On the other hand, maternal antibodies can decrease infant vaccine responses, a phenomenon named vaccine interference. The mechanisms underlying antibody-dependent immunity against pathogens and regulation of vaccine responses in early life remain poorly understood. This gap in knowledge limits the rationale design of maternal immunization strategies providing optimal protection to young infants. The overall aim of the project is to identify key biophysical (subclass and glycosylation profile) and functional features (activation of innate immune effectors) of transferred maternal antibodies mediating pathogen control and regulating vaccine responses in young infants. The project is focused on the two model pathogens selected for the whole program, pertussis and influenza. A systems serology approach will be used to characterize the functional properties of maternal antibodies transferred to the newborn following immunization during pregnancy and the impact of maternal immunization on the quality of infant vaccine responses. Engineering of human antibodies and adoptive transfer to genetically deficient and humanized mice will be used to determine the role of specific biophysical features of transferred maternal antibodies and of their interactions with infant IgG Fc receptors and complement in the control of pathogens and in the regulation of vaccine responses. Synergizing with Projects 1 and 2, Project 3 will provide mechanistic insight in the functional implications of the regulation of vaccine responses by pregnancy, the selective transfer of maternal antibodies across the placenta and their decay after birth for immunity to pathogens in infancy. Synergizing with project 4, project 3 will define the functional implications of the interactions between transferred maternal antibodies and the infant immune system for vaccine responses in infancy. The knowledge gained through the project will provide unprecedented insight in the immunobiology of maternal and infant immunization and will inform the development of vaccines and monoclonal antibodies providing optimal protection against infectious diseases in early life.