A Highly Attenuated Panfilovirus VesiculoVax Vaccine Rapidly Protects Nonhuman Primates Against Marburg Virus and 3 Species of Ebola Virus

被引:9
作者
Woolsey, Courtney [1 ,2 ]
Borisevich, Viktoriya [1 ,2 ]
Agans, Krystle N. [1 ,2 ]
OToole, Rachel [1 ,2 ]
Fenton, Karla A. [1 ,2 ]
Harrison, Mack B. [1 ,2 ]
Prasad, Abhishek N. [1 ,2 ]
Deer, Daniel J. [1 ,2 ]
Gerardi, Cheryl [3 ]
Morrison, Nneka [3 ]
Cross, Robert W. [1 ,2 ]
Eldridge, John H. [3 ]
Matassov, Demetrius [3 ]
Geisbert, Thomas W. [1 ,2 ]
机构
[1] Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA
[3] Auro Vaccines, Dept Viral Vaccine Dev, 401 North Middletown Rd, Pearl River, NY 10965 USA
基金
美国国家卫生研究院;
关键词
panfilovirus vaccine; Sudan virus; Ebola virus; Marburg virus; recombinant vesicular stomatitis virus; DOUBLE-BLIND; IMMUNOGENICITY; INFECTION; DISEASE; SAFETY;
D O I
10.1093/infdis/jiad157
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the deadliest. The vaccine, Ervebo, was shown to rapidly protect humans against Ebola disease, but is indicated only for EBOV infections with limited cross-protection against other filoviruses. Whether multivalent formulations of similar recombinant vesicular stomatitis virus (rVSV)-based vaccines could likewise confer rapid protection is unclear.Methods Here, we tested the ability of an attenuated, quadrivalent panfilovirus VesiculoVax vaccine (rVSV-Filo) to elicit fast-acting protection against MARV, EBOV, SUDV, and BDBV. Groups of cynomolgus monkeys were vaccinated 7 days before exposure to each of the 4 viral pathogens. All subjects (100%) immunized 1 week earlier survived MARV, SUDV, and BDBV challenge; 80% survived EBOV challenge. Survival correlated with lower viral load, higher glycoprotein-specific immunoglobulin G titers, and the expression of B-cell-, cytotoxic cell-, and antigen presentation-associated transcripts.Conclusions These results demonstrate multivalent VesiculoVax vaccines are suitable for filovirus outbreak management. The highly attenuated nature of the rVSV-Filo vaccine may be preferable to the Ervebo "delta G" platform, which induced adverse events in a subset of recipients.
引用
收藏
页码:S660 / S670
页数:11
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