Engineering tetravalent IgGs with enhanced agglutination potencies for trapping vigorously motile sperm in mucin matrix.

ABSTRACT: Multivalent antibodies such as sIgA can crosslink motile entities such as sperm and bacteria, creating agglomerates that are too large to permeate the dense mucin matrix in mucus, a process commonly referred to as immune exclusion. Unfortunately, sIgA remains challenging to produce in large quantities, and easily aggregates, which prevented their use in clinical applications. To develop sIgA-like tetravalent antibodies that are stable and can be easily produced in large quantities, we designed two IgGs possessing 4 identical Fab domains, with the Fabs arranged either in serial or in the diametrically opposite orientation. As a proof-of-concept, we engineered these tetravalent IgG constructs to bind a ubiquitous sperm antigen using a Fab previously isolated from an immune infertile woman. B

SUBMITTER: Shrestha B 

PROVIDER: S-EPMC8778962 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature