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

Autor: Cross RW; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Xu R; Department of Immunology., Matassov D; Department of Viral Vaccine Development, and., Hamm S; Department of Viral Vaccine Discovery, Profectus BioSciences Inc., Pearl River, New York, USA., Latham TE; Department of Viral Vaccine Development, and., Gerardi CS; Department of Viral Vaccine Development, and., Nowak RM; Department of Viral Vaccine Discovery, Profectus BioSciences Inc., Pearl River, New York, USA., Geisbert JB; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Ota-Setlik A; Department of Immunology., Agans KN; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Luckay A; Department of Immunology., Witko SE; Department of Viral Vaccine Development, and., Soukieh L; Department of Immunology., Deer DJ; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Mire CE; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Feldmann H; Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA., Happi C; Department of Biological Sciences and African Center of Excellence for Genomics of Infectious Diseases, Redeemer's University, Edo, Nigeria., Fenton KA; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA., Eldridge JH; Department of Immunology.; Department of Viral Vaccine Development, and.; Department of Viral Vaccine Discovery, Profectus BioSciences Inc., Pearl River, New York, USA., Geisbert TW; Galveston National Laboratory and.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2020 Jan 02; Vol. 130 (1), pp. 539-551.
DOI: 10.1172/JCI131958
Abstrakt: 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.
Databáze: MEDLINE