# Mechanistic insights into the kinetics of Fc receptor-mediated placental antibody transfer to optimize maternal vaccine strategies

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $404,479

## Abstract

ABSTRACT
Infants are vulnerable to infection due to their tolerogenic immune phenotype and limited adaptive
immune memory, which has limited the success of newborn vaccines. Trans-placental transfer of
immunoglobulin G (IgG) from mother to fetus provides crucial protection in the first weeks of life.
As such, maternal immunization has been implemented as a public health strategy to protect
infants against serious infections early in life. The neonatal Fc receptor (FcRn) plays a well-
defined role by binding to IgG and transporting it across the placental syncytiotrophoblast to the
stroma, which is followed by transport across the fetal capillary endothelium to the fetus, but
emerging evidence suggests low-affinity Fc gamma receptors FcγRIIb and FcγRIIIa might co-
regulate IgG transfer with FcRn. However, their role is less established and is often debated. As
the placenta develops with pregnancy progression, IgG transfer efficiency dynamically evolves
and fetal IgG concentrations at full-term pregnancy surpass maternal levels. Despite partial
success of maternal vaccines in reducing the occurance of some neonatal infections, current
vaccines do not provide comparable protection across pregnancies with varying gestational
length, placental and maternal immune features. Progress in this field has been limited by stark
inter-species differences in placental transfer confounding insights from rodent models, which is
exacerbated by the important regulatory challenges of studies involving pregnant women. A
mathematical mechanistic model of transplacental antibody transfer presents a novel alternative,
which takes individual maternal and placental information and predicts antibody levels in the
newborn. Our long-term goal is to realize the promise of personalized vaccines for mothers to
maximally immunize newborns. To achieve this goal, in this application, we will (i) identify the key
Fc receptors (FcR) and the mechanisms by which they mediate transfer through placental cellular
layers, (ii) determine antibody Fc features that best synergize with these FcR kinetics such as IgG
subclass and Fc N-glycosylation, and (iii) develop and validate a mechanistic model of IgG
transfer that combines these insights toward an in silico vaccine testbed. Our in-silico testing
platform will pave the way for rational design of vaccines, which is capable of saving tremendous
effort and budget for vaccine clinical trials by avoiding predictable low-efficacy strategies.

## Key facts

- **NIH application ID:** 10947500
- **Project number:** 1R01AI184565-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Sepideh Dolatshahi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $404,479
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947500

## Citation

> US National Institutes of Health, RePORTER application 10947500, Mechanistic insights into the kinetics of Fc receptor-mediated placental antibody transfer to optimize maternal vaccine strategies (1R01AI184565-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10947500. Licensed CC0.

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