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Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected
Olivier Reynard1, Frédéric Jacquot2, Gwénaëlle Evanno3
1Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale supérieure de Lyon, Lyon, France.
Plos One
|June 10, 2016
Summary
Low immunogenicity IgGs lacking specific sugar epitopes show promise for treating Ebola virus (EBOV) infection. These modified antibodies offer a potential new strategy for passive immunotherapy against EBOV disease.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Polyclonal xenogenic IgGs are vital for treating infectious diseases but can be highly immunogenic, limiting new applications.
- Key human xenogeneic antigens on IgG glycans, like α1-3 Galactose and Neu5Gc, can trigger immune responses.
- IgGs lacking these immunogenic sugar epitopes may offer an advantage for passive immunotherapy.
Purpose of the Study:
- To investigate the protective effect of low immunogenicity IgGs against Ebola virus (EBOV) infection in a guinea pig model.
- To assess if removing α1-3 Galactose and Neu5Gc from IgGs enhances their therapeutic potential for EBOV.
Main Methods:
- A double knock-out pig lacking α1-3 Galactose and Neu5Gc was immunized with EBOV glycoprotein (GP) virus-like particles.
- Hyper-immune polyclonal IgGs were purified and characterized for anti-EBOV GP and virus neutralizing titers.
- Guinea pigs were treated with these modified IgGs or control IgGs post-EBOV infection.
Main Results:
- The anti-EBOV IgGs demonstrated high titers (1:100,000 for anti-GP, 1:100 for neutralization).
- Animals treated with modified IgGs showed significantly prolonged survival compared to controls.
- A decreased virus load in the blood was observed on day 3 in the treated group.
Conclusions:
- IgGs lacking α1-3 Galactose and Neu5Gc exhibit a protective effect against EBOV infection.
- These modified IgGs represent a promising approach for passive immunotherapy in EBOV treatment.
- Reducing immunogenic epitopes on IgGs can enhance their therapeutic efficacy.
