Format

Send to

Choose Destination
PLoS One. 2016 Jun 9;11(6):e0156775. doi: 10.1371/journal.pone.0156775. eCollection 2016.

Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs.

Author information

1
Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale supérieure de Lyon, Lyon, France.
2
Inserm-Jean Mérieux BSL4 Laboratory, US003 Inserm, Lyon, France.
3
Xenothera, Nantes, France.
4
INSERM, UMR 1064, Nantes, France.
5
CHU de Nantes, ITUN, Nantes, France.
6
Université de Nantes, Nantes, France.
7
IECM, EA4644 Université de Nantes, ONIRIS, USC1383 INRA, Nantes, France.
8
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.
9
Avantea Foundation, Cremona, Italy.
10
Chemistry Department, University of Manitoba, Winnipeg, Canada.
11
Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia, Italy.

Abstract

Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example α1-3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking α1-3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper-immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking α1-3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection.

PMID:
27280712
PMCID:
PMC4900587
DOI:
10.1371/journal.pone.0156775
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center