Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge.

Autor: Tretyakova I; Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA. Electronic address: itretyakova@medigen-usa.com., Plante KS; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Rossi SL; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Lawrence WS; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Peel JE; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Gudjohnsen S; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Wang E; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Mirchandani D; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Tibbens A; Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA., Lamichhane TN; Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA., Lukashevich IS; Department of Pharmacology and Toxicology, University of Louisville, 505 S Hancock St., Louisville, KY 40202, USA., Comer JE; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Weaver SC; Institute for Human Infections and Immunity and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA., Pushko P; Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA. Electronic address: ppushko@medigen-usa.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2020 Apr 09; Vol. 38 (17), pp. 3378-3386. Date of Electronic Publication: 2020 Feb 19.
DOI: 10.1016/j.vaccine.2020.02.007
Abstrakt: Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. The population of V4020 vaccine virus derived from pMG4020-transfected Vero cells was characterized by next generation sequencing (NGS) and indicated no detectable genetic reversions. Cynomolgus macaques were vaccinated with V4020 vaccine virus. After one or two vaccinations including by intramuscular route, high levels of virus-neutralizing antibodies were confirmed with no viremia or apparent adverse reactions to vaccinations. The protective effect of vaccination was evaluated using an aerosol challenge with VEEV. After challenge, macaques had no detectable viremia, demonstrating a protective effect of vaccination with live V4020 VEEV vaccine.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AT, IT, and PP are Medigen employees. IT and PP are Medigen shareholders.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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