Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with andes virus

Kyle S. Brown, David Safronetz, Andrea Marzi, Hideki Ebihara, Heinz Feldmann

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)12781-12791
Number of pages11
JournalJournal of Virology
Volume85
Issue number23
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

Hantavirus
Vesiculovirus
Vesicular Stomatitis
lethal genes
hamsters
Cricetinae
Vaccines
vaccines
Viruses
Sin Nombre virus
Hantavirus Pulmonary Syndrome
Membrane Glycoproteins
neutralization
glycoproteins
animal disease models
Hantavirus Infections
Animal Disease Models
lethal dose
seroconversion
virus replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with andes virus. / Brown, Kyle S.; Safronetz, David; Marzi, Andrea; Ebihara, Hideki; Feldmann, Heinz.

In: Journal of Virology, Vol. 85, No. 23, 01.12.2011, p. 12781-12791.

Research output: Contribution to journalArticle

Brown, Kyle S. ; Safronetz, David ; Marzi, Andrea ; Ebihara, Hideki ; Feldmann, Heinz. / Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with andes virus. In: Journal of Virology. 2011 ; Vol. 85, No. 23. pp. 12781-12791.
@article{f3319741a2be4945b9007b063ae82b69,
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.",
author = "Brown, {Kyle S.} and David Safronetz and Andrea Marzi and Hideki Ebihara and Heinz Feldmann",
year = "2011",
month = "12",
day = "1",
doi = "10.1128/JVI.00794-11",
language = "English (US)",
volume = "85",
pages = "12781--12791",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with andes virus

AU - Brown, Kyle S.

AU - Safronetz, David

AU - Marzi, Andrea

AU - Ebihara, Hideki

AU - Feldmann, Heinz

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=81255173592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81255173592&partnerID=8YFLogxK

U2 - 10.1128/JVI.00794-11

DO - 10.1128/JVI.00794-11

M3 - Article

C2 - 21917979

AN - SCOPUS:81255173592

VL - 85

SP - 12781

EP - 12791

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -