# Immune correlates of tuberculosis and non-tuberculosis infectious morbidity in Southern African HIV-exposed, uninfected infants.

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $636,736

## Abstract

PROJECT SUMMARY/ABSTRACT
Over one million infants born to women living with HIV are spared from vertical HIV acquisition. This public
health success is attributable to scaling up of maternal antiretroviral treatment (ART), with current World Health
Organization (WHO) policies recommending lifetime ART for persons living with HIV, including pregnant
women. Yet, HIV-exposed uninfected (HEU) infants in resource-constrained settings experience 2- to 4-fold
higher infectious cause morbidity and mortality compared with HIV-unexposed (HU) infants in the same
settings. This is primarily due to diarrheal disease and respiratory illness, including tuberculosis (TB). HEU
children also experience 20-fold increased incidence of latent TB infection (LTBI) compared with HIV-
unexposed (HU) children. Several studies have described immune abnormalities among HEU children, which
might explain a portion of HEU infant vulnerability. In both Botswana and South Africa, also settings with high
TB and HIV prevalence, bacille Calmette-Guérin (BCG) immunization rates at birth exceed 98%. While some
studies have shown that BCG vaccination protects against TB meningitis and disseminated TB in HU infants
and may have heterologous effects that extend beyond TB protection, the reported alterations in HEU infant
immunity may impact the efficacy of the BCG vaccine both in directly protecting against TB and in providing the
non-specific immune protection. Leveraging two existing prospective observational maternal-child health
studies underway in Botswana and South Africa, respectively, each of which is following both HEU and HU
infants from birth and beyond infancy, we will use data and specimens from 900 infants (600 HEU infants) to
evaluate BCG vaccine-induced specific and non-specific immune responses while using immunological studies
to assess correlates of BCG vaccine protection. Specifically, we will 1) Define TB-related and TB-
independent causes of morbidity and mortality in BCG vaccinated HEU and HU infants; 2) Define
immune correlates of risk for tuberculosis infection in HEU infants using polychromatic flow cytometry to
compare conventional and unconventional T-cell responses to BCG vaccination; 3) Explore the effect of HIV
exposure on BCG-induced peripheral blood monocytes. We anticipate that study findings will inform TB
vaccine development for HEU infants,and might identify further potential interventions to protect against
infectious morbidity and mortality more frequently experienced by this vulnerable population of infants.

## Key facts

- **NIH application ID:** 9872117
- **Project number:** 5R01AI142670-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Kathleen Powis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $636,736
- **Award type:** 5
- **Project period:** 2019-02-13 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872117

## Citation

> US National Institutes of Health, RePORTER application 9872117, Immune correlates of tuberculosis and non-tuberculosis infectious morbidity in Southern African HIV-exposed, uninfected infants. (5R01AI142670-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872117. Licensed CC0.

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