Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death
Robert W. Cross, … , John H. Eldridge, Thomas W. Geisbert
Robert W. Cross, … , John H. Eldridge, Thomas W. Geisbert
Published October 22, 2019
Citation Information: J Clin Invest. 2020;130(1):539-551. https://doi.org/10.1172/JCI131958.
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Research Article Virology

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

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.

Authors

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

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Figure 2

Filovirus and LASV GP–specific IgG ELISA titers in macaques immunized with the quadrivalent vaccine.

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Filovirus and LASV GP–specific IgG ELISA titers in macaques immunized wi...
At study days 0 and 56, macaques were immunized i.m. with 4 × 107 PFU of the quadrivalent vaccine (black circles) or rVSV N4CT1-HIVgag as control (gray squares). A total of 20 vaccinated animals and 12 control animals are represented, except as noted. At study days 0, 10, 28 (only from SUDV and MARV challenge monkeys), 56, and 66, sera were collected and tested for (A) LASV GP–, (B) EBOV GP–, (C) SUDV GP–, and (D) MARV GP–specific IgG responses by ELISA. Data represent the geometric mean of log-transformed LASV and filovirus GP–specific IgG endpoint titer, with the 95% confidence interval. An unpaired 2-tailed t test was used to determine statistically significant differences (*P <0.05, **P < 0.005, ***P < 0.0005) between quadrivalent and control groups as indicated. Mean values and standard deviations are depicted in red.