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
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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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 4

Filovirus and LASV GP–specific IFNG ELISPOT responses in macaques immunized with the quadrivalent vaccine.

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Filovirus and LASV GP–specific IFNG ELISPOT responses in macaques immuni...
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, 56, and 66, PBMCs were collected and tested for LASV GP–, EBOV GP–, SUDV GP–, and MARV GP–peptide pool-specific IFNG secretion by ELISPOT assay. Data represent the average LASV GP–, EBOV GP–, SUDV GP–, or MARV GP–specific IFNG ELISPOT response, with the standard error of the mean indicated. The ratio number represents the responder rate of the animals with an antigen-specific IFNG ELISPOT response greater than or equal to 25 SFC/106 PBMCs. An unpaired 2-tailed t test was used to determine statistically significant differences (*P < 0.05, **P < 0.005) between quadrivalent and control groups, as indicated. Mean values and standard deviations are depicted in red.