# Antibody-dependent cellular phagocytosis by human breastmilk leukocytes: impact of antibody class, stage of lactation, and target size

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $63,895

## Abstract

Project Summary
 Mother-to-child transmission (MTCT) of HIV remains a crisis in resource-limited countries where HIV is
prevalent. Approximately 200,000 MTCTs of HIV occur annually, with as many as half of infections being due
to exposure via breastmilk (BM) [1, 2]. Yet, only ~10-15% of infants breastfed by HIV-infected mothers actually
become infected, suggesting a strong protective effect of BM itself [1-5]. Though multiple studies have
demonstrated the protective effect of human BM against HIV MTCT [1-10], the contribution of the milk’s cellular
component has been relatively overlooked, despite evidence that maternal leukocytes are functional beyond
the sites of ingestion [11-15]. The only clinical HIV vaccine trial to show efficacy, RV144, and many other
studies have correlated activities mediated by the constant (Fc) Ab domain with protection from HIV acquisition
and this is documented similarly with other pathogens [16-29]. Though demonstrated as necessary for the
clearance of numerous viral infections, one essential Fc-mediated response--Ab-dependent cellular
phagocytosis (ADCP)--has been relatively understudied in the context of HIV, particularly in the case of
prevention of MTCT [30-37]. Colostral phagocytes can perform ADCP of bacteria, parasites and yeast
opsonized with maternal Abs; however, this has not been studied with regard to HIV or HIV-infected cells [38-
44]. Furthermore, the potential contribution of ADCP to protection from MTCT of HIV has not been studied with
regard to impact of phagocytic target size (e.g., cell-free and cell-associated virus), or the effects of the
dynamic leukocyte composition of BM over the lactation period [45-50]. Only conflicting and/or small studies
have been conducted regarding the relevance of Ab subclass in Fc-mediated activity, especially in BM [16, 42,
51-57]. Given the substantial gap in present knowledge of the potential contribution of ADCP activity by BM
phagocytes to prevention of MTCT of HIV, it is critical to develop a multidimensional, comprehensive
understanding of ADCP by the relevant primary cells in BM. The proposed study aims to fill this knowledge
gap. AIM 1 will address the impact of phagocytic target size/type on ADCP by BM cells, AIM 2 will address the
impact of Ab class on ADCP by BM cells, and AIM 3 will address the impact of BM maturation over time on
ADCP activity. These data will allow the field to better understand the potential contribution of ADCP mediated
by BM cells to the reduction of MTCT of HIV, and may well be applicable to other pathogens that threaten
infants over the course of lactation.

## Key facts

- **NIH application ID:** 10222911
- **Project number:** 3R21HD095772-02S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Rebecca Powell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $63,895
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222911

## Citation

> US National Institutes of Health, RePORTER application 10222911, Antibody-dependent cellular phagocytosis by human breastmilk leukocytes: impact of antibody class, stage of lactation, and target size (3R21HD095772-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10222911. Licensed CC0.

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