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Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.
Matassov, Demetrius; Mire, Chad E; Latham, Theresa; Geisbert, Joan B; Xu, Rong; Ota-Setlik, Ayuko; Agans, Krystle N; Kobs, Dean J; Wendling, Morgan Q S; Burnaugh, Amanda; Rudge, Thomas L; Sabourin, Carol L; Egan, Michael A; Clarke, David K; Geisbert, Thomas W; Eldridge, John H.
Affiliation
  • Matassov D; Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, New York, USA dmatassov@profectusbiosciences.com.
  • Mire CE; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
  • Latham T; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Geisbert JB; Department of Virology and Vaccine Vectors, Profectus BioSciences Inc., Pearl River, New York, USA.
  • Xu R; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
  • Ota-Setlik A; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Agans KN; Department of Immunology, Profectus BioSciences Inc., Pearl River, New York, USA.
  • Kobs DJ; Department of Immunology, Profectus BioSciences Inc., Pearl River, New York, USA.
  • Wendling MQS; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
  • Burnaugh A; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Rudge TL; Battelle Memorial Institute, Columbus, Ohio, USA.
  • Sabourin CL; Battelle Memorial Institute, Columbus, Ohio, USA.
  • Egan MA; Battelle Memorial Institute, Columbus, Ohio, USA.
  • Clarke DK; Battelle Memorial Institute, Columbus, Ohio, USA.
  • Geisbert TW; Battelle Memorial Institute, Columbus, Ohio, USA.
  • Eldridge JH; Department of Immunology, Profectus BioSciences Inc., Pearl River, New York, USA.
J Virol ; 92(3)2018 02 01.
Article in En | MEDLINE | ID: mdl-29142131
ABSTRACT
Previous studies demonstrated that a single intramuscular (i.m.) dose of an attenuated recombinant vesicular stomatitis virus (rVSV) vector (VesiculoVax vector platform; rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHPs) from lethal challenge with EBOV strains Kikwit and Makona. Here, we studied the immunogenicities of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies, an optimal attenuated trivalent rVSV vector formulation was identified that included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV), and the Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were vaccinated with a single dose of the trivalent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 postvaccination, a serum IgG response specific for all three GPs was detected in all the vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP was also detected in a majority of the vaccinated macaques. No matter the level of total GP-specific immune response detected postvaccination, all the vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against the filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.IMPORTANCE The West African Ebola virus Zaire outbreak in 2013 showed that the disease was not only a regional concern, but a worldwide problem, and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens, like Ebola virus Sudan and Marburg, also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended trivalent filovirus vaccine that elicited a balanced immune response when administered as a single dose and provided complete protection against a lethal challenge with all three filovirus pathogens.
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Full text: 1 Collection: 01-internacional Topics: Acesso_medicamentos_insumos_estrategicos Health context: 1_ASSA2030 / 2_ODS3 Database: MEDLINE Main subject: Viral Vaccines / Glycoproteins / Vesiculovirus / Hemorrhagic Fever, Ebola / Ebolavirus / Marburgvirus / Marburg Virus Disease Type of study: Prognostic_studies Limits: Animals Language: En Journal: J Virol Year: 2018 Document type: Article

Full text: 1 Collection: 01-internacional Topics: Acesso_medicamentos_insumos_estrategicos Health context: 1_ASSA2030 / 2_ODS3 Database: MEDLINE Main subject: Viral Vaccines / Glycoproteins / Vesiculovirus / Hemorrhagic Fever, Ebola / Ebolavirus / Marburgvirus / Marburg Virus Disease Type of study: Prognostic_studies Limits: Animals Language: En Journal: J Virol Year: 2018 Document type: Article