Anti-EBOV GP IgGs Lacking alpha 1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs

作者：Reynard Olivier; Jacquot Frederic; Evanno Gwenalle; Mai Hoa Le; Salama Apolline; Martinet Bernard; Duvaux Odile; Bach Jean Marie; Conchon Sophie; Judor Jean Paul; Perota Andrea; Lagutina Irina; Duchi Roberto; Lazzari Giovanna; Le Berre Ludmilla; Perreault Helene; Lheriteau Elsa; Raoul Herve; Volchkov Viktor; Galli Cesare; Soulillou Jean Paul

来源：PLos One, 2016, 11(6): e0156775.

DOI：10.1371/journal.pone.0156775

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 alpha 1-3 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 alpha 1-3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyperimmune 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 alpha 1-3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection.

• 出版日期2016-6-9