Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death

Robert W. Cross, Rong Xu, Demetrius Matassov, Stefan Hamm, Theresa E. Latham, Cheryl S. Gerardi, Rebecca M. Nowak, Joan B. Geisbert, Ayuko Ota-Setlik, Krystle N. Agans, Amara Luckay, Susan E. Witko, Lena Soukieh, Daniel J. Deer, Chad E. Mire, Heinz Feldmann, Christian Happi, Karla A. Fenton, John H. Eldridge, Thomas W. Geisbert

Research output: Contribution to journalArticle

Abstract

Recent occurrences of filoviruses and the arenavirus Lassa virus (LASV) in overlapping endemic areas of Africa highlight the need for a prophylactic vaccine that would confer protection against all of these viruses that cause lethal hemorrhagic fever (HF). We developed a quadrivalent formulation of VesiculoVax that contains recombinant vesicular stomatitis virus (rVSV) vectors expressing filovirus glycoproteins and that also contains a rVSV vector expressing the glycoprotein of a lineage IV strain of LASV. Cynomolgus macaques were vaccinated twice with the quadrivalent formulation, followed by challenge 28 days after the boost vaccination with each of the 3 corresponding filoviruses (Ebola, Sudan, Marburg) or a heterologous contemporary lineage II strain of LASV. Serum IgG and neutralizing antibody responses specific for all 4 glycoproteins were detected in all vaccinated animals. A modest and balanced cell-mediated immune response specific for the glycoproteins was also detected in most of the vaccinated macaques. Regardless of the level of total glycoprotein-specific immune response detected after vaccination, all immunized animals were protected from disease and death following lethal challenges. These findings indicate that vaccination with attenuated rVSV vectors each expressing a single HF virus glycoprotein may provide protection against those filoviruses and LASV most commonly responsible for outbreaks of severe HF in Africa.

Original languageEnglish (US)
Pages (from-to)539-551
Number of pages13
JournalJournal of Clinical Investigation
Volume130
Issue number1
DOIs
StatePublished - Jan 2 2020

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Viral Hemorrhagic Fevers
Lassa virus
Primates
Glycoproteins
Vaccines
Vesicular Stomatitis
Viruses
Vaccination
Fever
Macaca
Arenavirus
Sudan
Neutralizing Antibodies
Antibody Formation
Disease Outbreaks
Immunoglobulin G
Serum

ASJC Scopus subject areas

  • Medicine(all)

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Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death. / Cross, Robert W.; Xu, Rong; Matassov, Demetrius; Hamm, Stefan; Latham, Theresa E.; Gerardi, Cheryl S.; Nowak, Rebecca M.; Geisbert, Joan B.; Ota-Setlik, Ayuko; Agans, Krystle N.; Luckay, Amara; Witko, Susan E.; Soukieh, Lena; Deer, Daniel J.; Mire, Chad E.; Feldmann, Heinz; Happi, Christian; Fenton, Karla A.; Eldridge, John H.; Geisbert, Thomas W.

In: Journal of Clinical Investigation, Vol. 130, No. 1, 02.01.2020, p. 539-551.

Research output: Contribution to journalArticle

Cross, RW, Xu, R, Matassov, D, Hamm, S, Latham, TE, Gerardi, CS, Nowak, RM, Geisbert, JB, Ota-Setlik, A, Agans, KN, Luckay, A, Witko, SE, Soukieh, L, Deer, DJ, Mire, CE, Feldmann, H, Happi, C, Fenton, KA, Eldridge, JH & Geisbert, TW 2020, 'Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death', Journal of Clinical Investigation, vol. 130, no. 1, pp. 539-551. https://doi.org/10.1172/JCI131958
Cross, Robert W. ; Xu, Rong ; Matassov, Demetrius ; Hamm, Stefan ; Latham, Theresa E. ; Gerardi, Cheryl S. ; Nowak, Rebecca M. ; Geisbert, Joan B. ; Ota-Setlik, Ayuko ; Agans, Krystle N. ; Luckay, Amara ; Witko, Susan E. ; Soukieh, Lena ; Deer, Daniel J. ; Mire, Chad E. ; Feldmann, Heinz ; Happi, Christian ; Fenton, Karla A. ; Eldridge, John H. ; Geisbert, Thomas W. / Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death. In: Journal of Clinical Investigation. 2020 ; Vol. 130, No. 1. pp. 539-551.
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