The Immunologic Impact of In Utero Malaria Exposure and Prenatal Chemoprevention

Malaria in pregnancy is estimated to affect more than 12 million women globally, leading to a range of adverse birth outcomes including low birth weight, stillbirths, maternal anemia, and intrauterine growth restriction. The only currently available malaria vaccine has demonstrated limited immunogenicity in children living in malaria-endemic settings. Children born to mothers with placental malaria have been reported to be at increased risk of malaria during the first years of life. Recent studies have revealed compelling evidence of fetal tolerance to malaria antigens, suggesting a potential immunologic mechanism for this association. Altered innate and adaptive immune responses following in utero malaria exposure have been documented after birth. A tolerant, or immunoregulatory, T cell phenotype has been identified in the cord blood of infants exposed to placental malaria. Furthermore, some studies have shown that infants born to mothers with placental malaria exhibit diminished responses to routine childhood vaccinations.

Therefore, the prevention of placental malaria-induced immune tolerance through enhanced chemoprevention holds the potential to improve both malaria-specific and global immune responses during early childhood. The goal of this K23 proposal is to test the hypothesis that in utero malaria infection induces tolerogenic fetal malaria-specific and global immune responses, and that these responses can be inhibited by enhanced prenatal malaria chemoprevention.

To achieve the aims of this study, the research team will leverage existing infrastructure and samples from a cohort of mother-infant pairs enrolled in an ongoing randomized clinical trial of highly effective artemisinin-based prenatal malaria chemoprevention in Uganda. The proposed studies will expand upon the candidate’s preliminary findings, which suggest the development of immunoregulatory responses in the cord blood of infants exposed to malaria in utero.

The candidate’s long-term career goal is to elucidate the biological mechanisms underlying infectious diseases that disproportionately affect impoverished populations and to apply these insights to address global health challenges. In this K23 application, the candidate presents a detailed research and career development plan aligned with these goals. She will receive further training in advanced immunology techniques, international collaborative research, and biostatistical analysis. The data generated and technical skills acquired through the execution of these aims will lay the foundation for a future R01 submission focused on evaluating host-pathogen interactions in malaria.

NIH project details

Drug-based Strategies
Immunology
Vaccines
Vulnerable Populations

Jul 2017 — Jun 2023

$1.05M

United States