Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. Our data suggest that prenatal exposure to parasitic infections can affect fetal immune constitution and functional antibody generation during subsequent vaccination in infancy. Transplacental trafficking of parasite antigens from mother to fetus occurs frequently, yielding multivalent T and B cell responses to parasite antigens at the time of birth. Fetal priming results in two phenotypes: either an enhanced response to the parasite antigens (“sensitized”) or a suppressed response (“tolerized”). The presence of parasitic infections is associated with lower infant IgG responses to Haemophilus influenzae and diphtheria antigens post-vaccination. In particular, response to diphtheria is reduced in malaria-tolerized infants, and the response to H. influenzae is impaired in filaria-tolerized infants. Mechanistic understanding of these immunophenotypes has been limited by an incomplete examination of infant T- and B-cell function. We propose here a detailed genomic and functional examination of T cell and B cell responses in cell samples biobanked from an existing, well-characterized cohort from Kenya, in order to determine how maternal parasitic infections and consequent sensitization or tolerization of infant immunity could influence early childhood responses to standard vaccination against H. influenzae, diphtheria, and Streptococcus pneumoniae.
This study will provide crucial preliminary mechanistic data for a larger, confirmatory study that will focus on the cellular mechanisms responsible for parasite-induced aberrations in vaccine response. It is likely that cellular pathways will differ among children who were or were not exposed during the antenatal period, and this information can be used to optimize policy on the timing and treatment for parasitic infections in the gestational period. It may also suggest the need for booster vaccinations in later childhood (after 12 months) among children born in parasite-endemic areas.
Funding for this project is provided by The Stanford Institute for Immunity, Transplantation and Infection (ITI) Interdisciplinary Research Awards Faculty Seed Grant