Evidence map›Paper›PMID 32937206›Full record

ArticleActa biomaterialia2020

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

Bhawana Shrestha, Alison Schaefer, Elizabeth C Chavez, Alexander J Kopp, Timothy M Jacobs, Thomas R Moench, Samuel K Lai

Open access · greenAbstract read
In one paragraph

Article in Acta biomaterialia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 47% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Bhawana ShresthaDepartment of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: bhawana@email.unc.edu.
Alison SchaeferUNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: amschaef@email.unc.edu.
Elizabeth C ChavezDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: ecchavez@bu.edu.
Alexander J KoppDepartment of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: alexkopp@unc.edu.
Timothy M JacobsDivision of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: timjacobs2@gmail.com.
Thomas R MoenchMucommune, LLC., Durham, NC 27709, United States. Electronic address: thomas.moench@mappbio.com.
Samuel K LaiDepartment of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Mucommune, LLC., Durham, NC 27709, United States. Electronic address: lai@unc.edu.
University of North Carolina at Chapel Hill · USUniversity of St. Thomas - Texas · US

Funding

Next Generation Multipurpose Prevention Technology: An Intravaginal Ring for HIV Prevention and Nonhormonal ContraceptionR01HD101344 · NICHD · OAK CREST INSTITUTE OF SCIENCE · PI BAUM, MARC MICHAEL, LAI, SAMUEL · 2020 to 2024
$3.7M
Engineering bispecific antibodies for non-hormonal contraceptionR01HD101562 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LAI, SAMUEL · 2020 to 2023
$2.1M
Preclinical Testing of Human Contraceptive Antibody (HCA) and HCA productsU54HD096957 · NICHD · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ANDERSON, DEBORAH J · 2018 to 2018
$2.0M
Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIVR44HD097063 · NICHD · MUCOMMUNE, LLC · PI KUSHIRO, KEIICHIRO · 2018 to 2022
$1.9M
Development of novel sperm-binding antibodiesR56HD095629 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LAI, SAMUEL · 2017 to 2017
$307k
Development of a biologic for non-hormonal contraceptionR43HD094454 · NICHD · MUCOMMUNE, LLC · PI CONE, RICHARD · 2018 to 2018
$213k
NICHD NIH HHS R01 HD101344NICHD NIH HHS R01 HD101562NICHD NIH HHS R43 HD094454NICHD NIH HHS R44 HD097063NICHD NIH HHS R56 HD095629NICHD NIH HHS U54 HD096957
6 · The paper itself

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. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG, while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscores the multimerization of IgG as a promising strategy to enhance antibody effector functions based on immune exclusion.

Indexed as

MucinsSperm AgglutinationAgglutinationAntibodiesFemaleHumansMaleSpermatozoaAntibodiesMucinsAgglutinationAntibodiesAntibody engineeringContraceptionSpermTetravalent IgG

Identifiers

PMID32937206
PMCPMC8778962
OpenAlexW3085615390

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.