Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine

D. M. Custer, E. Thompson, C. S. Schmaljohn, Thomas Ksiazek, J. W. Hooper

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the anti-bodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.

Original languageEnglish (US)
Pages (from-to)9894-9905
Number of pages12
JournalJournal of Virology
Volume77
Issue number18
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Hantavirus Pulmonary Syndrome
Sin Nombre virus
Hantavirus
DNA Vaccines
recombinant vaccines
Vaccination
vaccination
Genome
genome
Haplorhini
lethal genes
monkeys
Cricetinae
hamsters
Vaccines
vaccines
antiviral agents
Andes virus
Mesocricetus
Firearms

ASJC Scopus subject areas

  • Immunology

Cite this

Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. / Custer, D. M.; Thompson, E.; Schmaljohn, C. S.; Ksiazek, Thomas; Hooper, J. W.

In: Journal of Virology, Vol. 77, No. 18, 09.2003, p. 9894-9905.

Research output: Contribution to journalArticle

Custer, D. M. ; Thompson, E. ; Schmaljohn, C. S. ; Ksiazek, Thomas ; Hooper, J. W. / Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. In: Journal of Virology. 2003 ; Vol. 77, No. 18. pp. 9894-9905.
@article{b5f0772ac92847c896120c8cb131e867,
title = "Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine",
abstract = "Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50{\%}) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the anti-bodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100{\%} of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.",
author = "Custer, {D. M.} and E. Thompson and Schmaljohn, {C. S.} and Thomas Ksiazek and Hooper, {J. W.}",
year = "2003",
month = "9",
doi = "10.1128/JVI.77.18.9894-9905.2003",
language = "English (US)",
volume = "77",
pages = "9894--9905",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "18",

}

TY - JOUR

T1 - Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine

AU - Custer, D. M.

AU - Thompson, E.

AU - Schmaljohn, C. S.

AU - Ksiazek, Thomas

AU - Hooper, J. W.

PY - 2003/9

Y1 - 2003/9

N2 - Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the anti-bodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.

AB - Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the anti-bodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.

UR - http://www.scopus.com/inward/record.url?scp=0141458993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141458993&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.18.9894-9905.2003

DO - 10.1128/JVI.77.18.9894-9905.2003

M3 - Article

VL - 77

SP - 9894

EP - 9905

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 18

ER -