# The Immunologic Impact of In Utero Malaria Exposure and Prenatal Chemoprevention

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $199,379

## Abstract

Project Summary/Abstract
 Malaria in pregnancy is estimated to affect greater than 12 million women leading to a multitude of
adverse birth outcomes including low-birth weight, stillbirths, maternal anemia, and intrauterine growth
restriction. The only currently available malaria vaccine has been limited by poor immunogenicity in children
living in malaria-endemic settings. Children born to mothers with placental malaria have been reported to have
an increased risk of malaria in the first years of life. Recent studies have revealed intriguing evidence of fetal
tolerance to malaria antigens, suggesting a potential immunologic mechanism for this association. Altered
innate and adaptive immune responses after birth have been demonstrated following in utero malaria
exposure. A tolerant, or immunoregulatory, T cell phenotype has been described in the cord blood of placental
malaria-exposed infants. Additionally, some studies have found that infants born to mothers with placental
malaria have decreased response to routine childhood vaccinations. Therefore, prevention of placental
malaria-induced immune tolerance through enhanced chemoprevention has the potential to augment
longitudinal malaria-specific and global immunity 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 that are inhibited by enhanced prenatal malaria
chemoprevention. We will determine the immunologic consequences of in utero malaria exposure through the
following three aims: 1) To determine the effect of in utero malaria exposure and prenatal chemoprevention on
malaria-specific T-cell immune responses in early childhood. 2) To determine the effect of in utero malaria
exposure and prenatal chemoprevention on innate immune responses during malaria infection in early
childhood 3) To assess the impact of in utero malaria exposure on the immune response to routine
vaccination. To achieve these aims we 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 studies proposed in this application will build on the
candidate's preliminary findings suggesting the development of cord blood immunoregulatory responses
among in utero malaria-exposed infants.
 The candidate's career goal is to decipher the biologic underpinnings of infectious diseases that afflict
the impoverished, and to apply these findings to address global health challenges. In this K23 application, the
candidate has outlined a detailed research and career development plan tailored to match her career goals.
She will gain additional training in advanced techniques of immunology research, international collaborative
research, and biostatistical analysis. Data and technical training generated through the evaluation of the
proposed aims w...

## Key facts

- **NIH application ID:** 9952303
- **Project number:** 5K23AI127886-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Mary Prahl
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,379
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952303

## Citation

> US National Institutes of Health, RePORTER application 9952303, The Immunologic Impact of In Utero Malaria Exposure and Prenatal Chemoprevention (5K23AI127886-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952303. Licensed CC0.

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