title: Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus.
abstract: Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS). A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSVΔG/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSVΔG/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV G(N)/G(C) antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kyle S
authors.initials: KS
authors.lastname: Brown
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006476:Orthohantavirus / Q000276:immunology*; D018778:Hantavirus Infections / Q000235:genetics / Q000517:prevention & control* / Q000821:virology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008647:Mesocricetus / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014611:Vaccination; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D014765:Viral Vaccines