A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection

Wataru Akahata, Zhi Yong Yang, Hanne Andersen, Siyang Sun, Heather A. Holdaway, Wing Pui Kong, Mark G. Lewis, Stephen Higgs, Michael G. Rossmann, Srinivas Rao, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

Original languageEnglish (US)
Pages (from-to)334-338
Number of pages5
JournalNature Medicine
Volume16
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Virus-Like Particle Vaccines
Chikungunya virus
Alphavirus
Viruses
Primates
Virion
Infection
Neutralizing Antibodies
Immunization
Vaccines
Viral Structural Proteins
Kenya
Viremia
Haplorhini
Antiviral Agents
Public Health
Antibodies
Public health
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Akahata, W., Yang, Z. Y., Andersen, H., Sun, S., Holdaway, H. A., Kong, W. P., ... Nabel, G. J. (2010). A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nature Medicine, 16(3), 334-338. https://doi.org/10.1038/nm.2105

A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. / Akahata, Wataru; Yang, Zhi Yong; Andersen, Hanne; Sun, Siyang; Holdaway, Heather A.; Kong, Wing Pui; Lewis, Mark G.; Higgs, Stephen; Rossmann, Michael G.; Rao, Srinivas; Nabel, Gary J.

In: Nature Medicine, Vol. 16, No. 3, 03.2010, p. 334-338.

Research output: Contribution to journalArticle

Akahata, W, Yang, ZY, Andersen, H, Sun, S, Holdaway, HA, Kong, WP, Lewis, MG, Higgs, S, Rossmann, MG, Rao, S & Nabel, GJ 2010, 'A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection', Nature Medicine, vol. 16, no. 3, pp. 334-338. https://doi.org/10.1038/nm.2105
Akahata, Wataru ; Yang, Zhi Yong ; Andersen, Hanne ; Sun, Siyang ; Holdaway, Heather A. ; Kong, Wing Pui ; Lewis, Mark G. ; Higgs, Stephen ; Rossmann, Michael G. ; Rao, Srinivas ; Nabel, Gary J. / A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. In: Nature Medicine. 2010 ; Vol. 16, No. 3. pp. 334-338.
@article{d7ab1b157b0846408b64abd0eab35805,
title = "A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection",
abstract = "Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.",
author = "Wataru Akahata and Yang, {Zhi Yong} and Hanne Andersen and Siyang Sun and Holdaway, {Heather A.} and Kong, {Wing Pui} and Lewis, {Mark G.} and Stephen Higgs and Rossmann, {Michael G.} and Srinivas Rao and Nabel, {Gary J.}",
year = "2010",
month = "3",
doi = "10.1038/nm.2105",
language = "English (US)",
volume = "16",
pages = "334--338",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection

AU - Akahata, Wataru

AU - Yang, Zhi Yong

AU - Andersen, Hanne

AU - Sun, Siyang

AU - Holdaway, Heather A.

AU - Kong, Wing Pui

AU - Lewis, Mark G.

AU - Higgs, Stephen

AU - Rossmann, Michael G.

AU - Rao, Srinivas

AU - Nabel, Gary J.

PY - 2010/3

Y1 - 2010/3

N2 - Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

AB - Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

UR - http://www.scopus.com/inward/record.url?scp=77949264955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949264955&partnerID=8YFLogxK

U2 - 10.1038/nm.2105

DO - 10.1038/nm.2105

M3 - Article

C2 - 20111039

AN - SCOPUS:77949264955

VL - 16

SP - 334

EP - 338

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 3

ER -