Helminth- and Bacillus Calmette-Guérin-Induced Immunity in Children Sensitized In Utero to Filariasis and Schistosomiasis

Abstract

Abstract Infants and children are routinely vaccinated with bacillus Calmette-Guérin (BCG) in areas of the world where worm infections are common. Because maternal helminth infection during pregnancy can sensitize the developing fetus, we studied whether this prenatal immunity persists in childhood and modifies the immune response to BCG. Children and newborns living in rural Kenya, where BCG is administered at birth and filariasis and schistosomiasis are endemic, were examined. T cells from 2- to 10-year-old children of mothers without filariasis or schistosomiasis produced 10-fold more IFN-γ in response to mycobacterial purified protein derivative than children of helminth-infected mothers (p < 0.01). This relationship was restricted to purified protein derivative because maternal infection status did not correlate with filarial Ag-driven IL-2, IFN-γ, IL-4, or IL-5 responses by children. Prospective studies initiated at birth showed that helminth-specific T cell immunity acquired in utero is maintained until at least 10–14 mo of age in the absence of infection with either Wuchereria bancrofti or Schistosoma haematobium. Purified protein derivative-driven T cell IFN-γ production evaluated 10–14 mo after BCG vaccination was 26-fold higher for infants who were not sensitized to filariae or schistosomes in utero relative to subjects who experienced prenatal sensitization (p < 0.01). These data indicate that helminth-specific immune responses acquired during gestation persist into childhood and that this prenatal sensitization biases T cell immunity induced by BCG vaccination away from type 1 IFN-γ responses associated with protection against mycobacterial infection.