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. 2009 Jul;83(14):7296-304.
doi: 10.1128/JVI.00561-09. Epub 2009 Apr 22.

Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus

Thomas W Geisbert  1 , Joan B Geisbert, Anders Leung, Kathleen M Daddario-DiCaprio, Lisa E Hensley, Allen Grolla, Heinz Feldmann
Affiliations

Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus

Thomas W Geisbert et al. J Virol. 2009 Jul.

Abstract

The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVDeltaG/SEBOVGP, VSVDeltaG/ZEBOVGP, and VSVDeltaG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVDeltaG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species.

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Figures

FIG. 1.
FIG. 1.
Immunization and challenge of nonhuman primates. Flow chart (top) and table (bottom) of experimental design. Arrows indicate days of sampling. Cont, control group; Exp, experimental group; No., number of monkeys in group.
FIG. 2.
FIG. 2.
Immunization, challenge, and rechallenge of nonhuman primates. Flow chart (top) and table (bottom) of experimental design. Arrows indicate days of sampling. *, the two-injection VSV-based vaccine consisted of a recombinant VSV-based SEBOV vaccine and subsequently a combination of a recombinant VSV-based ZEBOV vaccine and a VSV-based MARV vaccine, given as indicated. For definitions of abbreviations, see the legend for Fig. 1.
FIG. 3.
FIG. 3.
Kaplan-Meier survival curves for cynomolgus macaques vaccinated with a blended recombinant VSV vaccine and challenged with CIEBOV, ZEBOV, or MARV at day 28 after vaccination (A) or with a blended recombinant VSV vaccine or a monovalent ZEBOV vaccine (*) and challenged with SEBOV at day 28 after vaccination (B).
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