Successful topical respiratory tract immunization of primates against Ebola virus

Alexander Bukreyev, Pierre E. Rollin, Mallory K. Tate, Lijuan Yang, Sherif R. Zaki, Wun Ju Shieh, Brian R. Murphy, Peter L. Collins, Anthony Sanchez

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in comL. Meyer and G. Donnert bination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys - in which HPIV3 infection is mild and asymptomatic - and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

Original languageEnglish (US)
Pages (from-to)6379-6388
Number of pages10
JournalJournal of Virology
Volume81
Issue number12
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Ebolavirus
Human parainfluenza virus 3
respiratory system
Respiratory System
Primates
Immunization
immunization
fever
Viral Hemorrhagic Fevers
viruses
Zaire Ebola virus
glycoproteins
Ebola Hemorrhagic Fever
Fever
Biological Warfare
Vaccines
immune response
bioterrorism
nucleocapsid proteins
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Bukreyev, A., Rollin, P. E., Tate, M. K., Yang, L., Zaki, S. R., Shieh, W. J., ... Sanchez, A. (2007). Successful topical respiratory tract immunization of primates against Ebola virus. Journal of Virology, 81(12), 6379-6388. https://doi.org/10.1128/JVI.00105-07

Successful topical respiratory tract immunization of primates against Ebola virus. / Bukreyev, Alexander; Rollin, Pierre E.; Tate, Mallory K.; Yang, Lijuan; Zaki, Sherif R.; Shieh, Wun Ju; Murphy, Brian R.; Collins, Peter L.; Sanchez, Anthony.

In: Journal of Virology, Vol. 81, No. 12, 06.2007, p. 6379-6388.

Research output: Contribution to journalArticle

Bukreyev, A, Rollin, PE, Tate, MK, Yang, L, Zaki, SR, Shieh, WJ, Murphy, BR, Collins, PL & Sanchez, A 2007, 'Successful topical respiratory tract immunization of primates against Ebola virus', Journal of Virology, vol. 81, no. 12, pp. 6379-6388. https://doi.org/10.1128/JVI.00105-07
Bukreyev, Alexander ; Rollin, Pierre E. ; Tate, Mallory K. ; Yang, Lijuan ; Zaki, Sherif R. ; Shieh, Wun Ju ; Murphy, Brian R. ; Collins, Peter L. ; Sanchez, Anthony. / Successful topical respiratory tract immunization of primates against Ebola virus. In: Journal of Virology. 2007 ; Vol. 81, No. 12. pp. 6379-6388.
@article{0a30a5cc9f11468f9d6d7e94a38f17ab,
title = "Successful topical respiratory tract immunization of primates against Ebola virus",
abstract = "Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in comL. Meyer and G. Donnert bination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys - in which HPIV3 infection is mild and asymptomatic - and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88{\%} of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.",
author = "Alexander Bukreyev and Rollin, {Pierre E.} and Tate, {Mallory K.} and Lijuan Yang and Zaki, {Sherif R.} and Shieh, {Wun Ju} and Murphy, {Brian R.} and Collins, {Peter L.} and Anthony Sanchez",
year = "2007",
month = "6",
doi = "10.1128/JVI.00105-07",
language = "English (US)",
volume = "81",
pages = "6379--6388",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Successful topical respiratory tract immunization of primates against Ebola virus

AU - Bukreyev, Alexander

AU - Rollin, Pierre E.

AU - Tate, Mallory K.

AU - Yang, Lijuan

AU - Zaki, Sherif R.

AU - Shieh, Wun Ju

AU - Murphy, Brian R.

AU - Collins, Peter L.

AU - Sanchez, Anthony

PY - 2007/6

Y1 - 2007/6

N2 - Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in comL. Meyer and G. Donnert bination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys - in which HPIV3 infection is mild and asymptomatic - and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

AB - Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in comL. Meyer and G. Donnert bination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys - in which HPIV3 infection is mild and asymptomatic - and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.

UR - http://www.scopus.com/inward/record.url?scp=34249946893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249946893&partnerID=8YFLogxK

U2 - 10.1128/JVI.00105-07

DO - 10.1128/JVI.00105-07

M3 - Article

VL - 81

SP - 6379

EP - 6388

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -