@article{f314b556d9604f4787af04fcefadb341,
title = "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.",
author = "Cross, {Robert W.} and Rong Xu and Demetrius Matassov and Stefan Hamm and Latham, {Theresa E.} and Gerardi, {Cheryl S.} and Nowak, {Rebecca M.} and Geisbert, {Joan B.} and Ayuko Ota-Setlik and Agans, {Krystle N.} and Amara Luckay and Witko, {Susan E.} and Lena Soukieh and Deer, {Daniel J.} and Mire, {Chad E.} and Heinz Feldmann and Christian Happi and Fenton, {Karla A.} and Eldridge, {John H.} and Geisbert, {Thomas W.}",
note = "Funding Information: The authors thank Kimberly Schuenke for administrative assistance, Viktoriya Borisevich for assistance with clinical pathology assays, Natalie Dobias for assistance with tissue preparations, and the UTMB Animal Resource Center for animal husbandry support. We also thank Pardis Sabeti, Robert Garry, and Luis Branco for assistance with obtaining the LASV isolate used in this study. This work was supported by Department of Health and Human Services/ National Institute of Allergy and Infectious Diseases (NIAID)/NIH contract number HHSN272201700077C (to JHE) and NIAID/NIH grant number UC7AI094660 (to UTMB for BSL-4 operations support of the Galveston National Laboratory). Some samples used to optimize assays were made available by NIAID/NIH grant number U19AI142785 (to TWG). Partial funding was provided through the NIAID/NIH Intramural Research Program (to HF). Support was also received from the National Human Genome Research Institute (NHGRI), NIH Department of Health and Human Services, under grant numbers U01HG007480 and U54HG007480 (to CH). World Bank project ACE019 supports CH{\textquoteright}s research at Redeemer{\textquoteright}s University, Ede, Nigeria. The opinions, interpretations, conclusions, and recommendations contained here are not necessarily endorsed by UTMB at Galveston or the NIH. Publisher Copyright: {\textcopyright} 2020 American Society for Clinical Investigation.",
year = "2020",
month = jan,
day = "2",
doi = "10.1172/JCI131958",
language = "English (US)",
volume = "130",
pages = "539--551",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",
}