Transferred Immunity

PROJECT 2 - ABSTRACT
This project proposes to better understand the mechanisms governing, and advance our ability to
rationally control maternal-fetal antibody transport. By comparing the profiles of antibodies from milk and from
blood samples during pregnancy and umbilical cord blood samples after birth using high-throughput proteomic
tools such as NextGen sequencing of the maternal B cell repertoire and high-resolution proteomic analysis by
mass spectrometry, IgG glycoprofiling, Fc receptor affinity characterization, and Ig isotyping and subclassing,
we will define phenotypic biases in global and antigen/ vaccine-specific Ab repertoires transferred to the fetus
in vaccinated and unvaccinated pregnancies, and quantify the degree of similarity of the antibody repertoire
between mother and child. In vivo evaluation of the relationship between antibody half-life and placental
transport in animal models using natural and engineered IgG variants will define the extent of linkage between
different biological roles of FcRn, and evaluation of existing and engineering of novel IgG Fc variants for
enhanced placental transport in the ex vivo human placenta model will be employed to identify Abs with altered
transport phenotypes. Our overarching hypotheses are that among natural and engineered antibody molecules
there exist intrinsic biases for certain antibody molecules to transport across placenta more and less efficiently.
Discovery and knowledge of these biases will contribute to development of vaccine and therapeutic antibody
strategies with increased or decreased transport efficiency that are designed to improve health outcomes for
mothers and the fetus/neonate during this critical period of immunological development.

Grant Number: 5U19AI145825-05
NIH Institute/Center: NIH
Principal Investigator: Margaret Ackerman