# Impact of HIV exposure, feeding status, and microbiome on immune ontogeny and vaccine responses in infants

> **NIH NIH U01** · STANFORD UNIVERSITY · 2021 · $420,985

## Abstract

PROJECT SUMMARY
Each year, approximately 8 million children under the age of five die, and approximately 3.3 million of those
deaths occur in the neonatal period. Infections are the single largest contributor to these deaths, accounting for
an estimated 36% of the mortality. However, our understanding of how the neonatal and infant immune system
influence this susceptibility to infectious diseases is limited. Thus, to elucidate mechanisms that regulate the
development of infant immunity, we propose evaluating immune development in a setting of high risk of
neonatal and infant infection. In particular, infants who are exposed to HIV, yet remain uninfected, suffer
increased rates of respiratory and diarrheal illnesses. Feeding status is also associated with altered risk of
infection, with exclusively breastfed children less likely to suffer diarrheal illness and death. Our preliminary
data suggest that both HIV exposure and feeding status influence the infant microbiome, which is increasingly
recognized for its important role in driving immune development. Thus, to better understand the unique
characteristics of immune development in neonates and infants, we propose evaluating the impact of HIV
exposure and feeding status on the interplay between the microbiome, innate and adaptive cellular immune
ontogeny, and vaccination outcomes. Our preliminary data also suggests that HIV exposure leads to
oligoclonality in the T cell repertoire, potentially narrowing the spectrum of antigens to which infant T cells can
respond. We have also found that HIV infection increases natural killer (NK) cell diversity while decreasing NK
cell cytotoxic function. Using longitudinal samples collected from HIV-exposed uninfected (HEU) and HIV-
unexposed (HU) babies in an area of extremely high HIV prevalence in South Africa, we will: 1) compare the T
and NK cell repertoires and function between HEU and HU babies, 2) determine the impact of maternal HIV,
feeding status, gut and breastmilk microbiome on the infant mucosal microbiome, and 3) build a predictive
model of effective pertussis and rotavirus vaccines to identify the major factors that associate with vaccine
success or failure. This study will provide a comprehensive understanding of how cellular immune responses
and the microbiome evolve in the first year of life and influence the ability to generate an effective cellular and
humoral immune responses.

## Key facts

- **NIH application ID:** 10116253
- **Project number:** 5U01AI131302-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Catherine A Blish
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,985
- **Award type:** 5
- **Project period:** 2017-03-11 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116253

## Citation

> US National Institutes of Health, RePORTER application 10116253, Impact of HIV exposure, feeding status, and microbiome on immune ontogeny and vaccine responses in infants (5U01AI131302-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10116253. Licensed CC0.

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