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

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

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.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Viral / blood*
  • Ebola Vaccines / immunology
  • Ebola Vaccines / therapeutic use*
  • Ebolavirus / immunology
  • Galactose / deficiency*
  • Guinea Pigs
  • Hemorrhagic Fever, Ebola / blood
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Immunoglobulin G / immunology*
  • Male
  • Neuraminic Acids / metabolism*
  • Swine
  • Vaccination
  • Viral Envelope Proteins / immunology*
  • Viral Load

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Viral
  • Ebola Vaccines
  • Immunoglobulin G
  • Neuraminic Acids
  • Viral Envelope Proteins
  • anti-IgG
  • envelope glycoprotein, Ebola virus
  • N-glycolylneuraminic acid
  • Galactose

Grant support

This work was supported by Institut national de la santé et de la recherche médicale (INSERM), Agence Nationale de la Recherche (ANR-14-EBOL-002-01) and the European Union FP7 project ANTIGONE (278976). The companies Xenothera and Avantea co-funded the study, and only provided financial support in the form of authors' salaries and/or research materials. The funders provided support in the form of salaries for authors AS, GE, AP, RD, and IL or consultance for JPS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.