title: Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates.
abstract: Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV.
authors: Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors: Andrea
authors: A
authors: Marzi
authors: Flora
authors: F
authors: Engelmann
authors: Friederike
authors: F
authors: Feldmann
authors: Kristen
authors: K
authors: Haberthur
authors: W Lesley
authors: WL
authors: Shupert
authors: Douglas
authors: D
authors: Brining
authors: Dana P
authors: DP
authors: Scott
authors: Thomas W
authors: TW
authors: Geisbert
authors: Yoshihiro
authors: Y
authors: Kawaoka
authors: Michael G
authors: MG
authors: Katze
authors: Heinz
authors: H
authors: Feldmann
authors: Ilhem
authors: I
authors: Messaoudi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D029024:Marburgvirus / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D019562:Viral Load / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D046129:Ebola Vaccines; C028391:G protein, vesicular stomatitis virus; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins