Single-dose trivalent VesiculoVax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge

Demetrius Matassov, Chad Mire, Theresa Latham, Joan B. Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N. Agans, Dean J. Kobs, Morgan Q.S. Wendling, Amanda Burnaugh, Thomas L. Rudge, Carol L. Sabourin, Michael A. Egan, David K. Clarke, Thomas Geisbert, John H. Eldridge

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere01190-17
JournalJournal of Virology
Volume92
Issue number3
DOIs
StatePublished - Feb 1 2018

Fingerprint

Marburgvirus
Ebolavirus
Filoviridae
Vesiculovirus
Vesicular Stomatitis
Macaca
Vaccines
glycoproteins
Glycoproteins
vaccines
Viruses
dosage
Sudan Ebola virus
Primates
Zaire Ebola virus
Angola
immune response
Democratic Republic of the Congo
Sudan
Africa South of the Sahara

Keywords

  • Attenuation
  • Challenge
  • Ebola virus vaccine
  • Glycoprotein
  • Marburg virus vaccine
  • Nonhuman primates
  • Protection
  • RVSV vector
  • Trivalent
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Matassov, D., Mire, C., Latham, T., Geisbert, J. B., Xu, R., Ota-Setlik, A., ... Eldridge, J. H. (2018). Single-dose trivalent VesiculoVax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge. Journal of Virology, 92(3), [e01190-17]. https://doi.org/10.1128/JVI.01190-17

Single-dose trivalent VesiculoVax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge. / Matassov, Demetrius; Mire, Chad; 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; Eldridge, John H.

In: Journal of Virology, Vol. 92, No. 3, e01190-17, 01.02.2018.

Research output: Contribution to journalArticle

Matassov, D, Mire, C, Latham, T, Geisbert, JB, Xu, R, Ota-Setlik, A, Agans, KN, Kobs, DJ, Wendling, MQS, Burnaugh, A, Rudge, TL, Sabourin, CL, Egan, MA, Clarke, DK, Geisbert, T & Eldridge, JH 2018, 'Single-dose trivalent VesiculoVax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge', Journal of Virology, vol. 92, no. 3, e01190-17. https://doi.org/10.1128/JVI.01190-17
Matassov, Demetrius ; Mire, Chad ; 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 ; Eldridge, John H. / Single-dose trivalent VesiculoVax vaccine protects macaques from lethal Ebolavirus and Marburgvirus challenge. In: Journal of Virology. 2018 ; Vol. 92, No. 3.
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