PLoS ONE (Jan 2016)

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

  • Olivier Reynard,
  • Frédéric Jacquot,
  • Gwénaëlle Evanno,
  • Hoa Le Mai,
  • Apolline Salama,
  • Bernard Martinet,
  • Odile Duvaux,
  • Jean-Marie Bach,
  • Sophie Conchon,
  • Jean-Paul Judor,
  • Andrea Perota,
  • Irina Lagutina,
  • Roberto Duchi,
  • Giovanna Lazzari,
  • Ludmilla Le Berre,
  • Hélène Perreault,
  • Elsa Lheriteau,
  • Hervé Raoul,
  • Viktor Volchkov,
  • Cesare Galli,
  • Jean-Paul Soulillou

DOI
https://doi.org/10.1371/journal.pone.0156775
Journal volume & issue
Vol. 11, no. 6
p. e0156775

Abstract

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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.