Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs.
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.
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.
Olivier
O
Reynard
Inserm-Jean Mérieux BSL4 Laboratory, US003 Inserm, Lyon, France.
Frédéric
F
Jacquot
Xenothera, Nantes, France.
Gwénaëlle
G
Evanno
INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
Hoa Le
HL
Mai
Xenothera, Nantes, France.
Apolline
http://orcid.org/0000-0002-3157-0749
A
Salama
INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
Bernard
B
Martinet
Xenothera, Nantes, France.
Odile
O
Duvaux
Xenothera, Nantes, France.|IECM, EA4644 Université de Nantes, ONIRIS, USC1383 INRA, Nantes, France.
Jean-Marie
JM
Bach
INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
Sophie
S
Conchon
INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
Jean-Paul
JP
Judor
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.
Andrea
A
Perota
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.
Irina
I
Lagutina
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.
Roberto
R
Duchi
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.|Avantea Foundation, Cremona, Italy.
Giovanna
G
Lazzari
INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
Ludmilla
L
Le Berre
Chemistry Department, University of Manitoba, Winnipeg, Canada.
Hélène
H
Perreault
Xenothera, Nantes, France.
Elsa
E
Lheriteau
Inserm-Jean Mérieux BSL4 Laboratory, US003 Inserm, Lyon, France.
Hervé
H
Raoul
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.
Viktor
V
Volchkov
Avantea, Laboratory of Reproductive Technologies, Cremona, Italy.|Avantea Foundation, Cremona, Italy.|Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia, Italy.
Cesare
C
Galli
Xenothera, Nantes, France.|Université de Nantes, Nantes, France.
Jean-Paul
JP
Soulillou
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood*; D046129:Ebola Vaccines / Q000276:immunology / Q000627:therapeutic use*; D029043:Ebolavirus / Q000276:immunology; D005690:Galactose / Q000172:deficiency*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D009438:Neuraminic Acids / Q000378:metabolism*; D013552:Swine; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load
D000888:Antibodies, Anti-Idiotypic; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D007074:Immunoglobulin G; D009438:Neuraminic Acids; D014759:Viral Envelope Proteins; C048844:anti-IgG; C113189:envelope glycoprotein, Ebola virus; C032592:N-glycolylneuraminic acid; D005690:Galactose