title: Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.
abstract: We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Mallory
authors.initials: M
authors.lastname: Willet
authors.forename: Amy B
authors.initials: AB
authors.lastname: Papaneri
authors.forename: Christoph
authors.initials: C
authors.lastname: Wirblich
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.forename: Michael
authors.initials: M
authors.lastname: Holbrook
authors.forename: Peter
authors.initials: P
authors.lastname: Jahrling
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D046129:Ebola Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D011819:Rabies Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D011820:Rabies virus / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D007074:Immunoglobulin G; D011819:Rabies Vaccines; D014763:Viral Matrix Proteins