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Vaccines and Antiviral Agents

A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge

Alexander Bukreyev, Lijuan Yang, Sherif R. Zaki, Wun-Ju Shieh, Pierre E. Rollin, Brian R. Murphy, Peter L. Collins, Anthony Sanchez
Alexander Bukreyev
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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  • For correspondence: abukreyev@niaid.nih.gov
Lijuan Yang
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Sherif R. Zaki
2National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Wun-Ju Shieh
2National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Pierre E. Rollin
2National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Brian R. Murphy
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Peter L. Collins
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
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Anthony Sanchez
2National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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DOI: 10.1128/JVI.80.5.2267-2279.2006
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ABSTRACT

To determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against Ebola virus (EV), recombinant human parainfluenza virus type 3 (HPIV3) was modified to express either the EV structural glycoprotein (GP) by itself (HPIV3/EboGP) or together with the EV nucleoprotein (NP) (HPIV3/EboGP-NP). Expression of EV GP by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in Vero cells. HPIV3/EboGP was 100-fold more efficiently neutralized by antibodies to EV than by antibodies to HPIV3. Guinea pigs infected with a single intranasal inoculation of 105.3 PFU of HPIV3/EboGP or HPIV3/EboGP-NP showed no apparent signs of disease yet developed a strong humoral response specific to the EV proteins. When these animals were challenged with an intraperitoneal injection of 103 PFU of EV, there were no outward signs of disease, no viremia or detectable EV antigen in the blood, and no evidence of infection in the spleen, liver, and lungs. In contrast, all of the control animals died or developed severe EV disease following challenge. The highly effective immunity achieved with a single vaccine dose suggests that intranasal immunization with live vectored vaccines based on recombinant respiratory viruses may be an advantageous approach to inducing protective responses against severe systemic infections, such as those caused by hemorrhagic fever agents.

  • Copyright © 2006 American Society for Microbiology
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A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge
Alexander Bukreyev, Lijuan Yang, Sherif R. Zaki, Wun-Ju Shieh, Pierre E. Rollin, Brian R. Murphy, Peter L. Collins, Anthony Sanchez
Journal of Virology Feb 2006, 80 (5) 2267-2279; DOI: 10.1128/JVI.80.5.2267-2279.2006

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A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge
Alexander Bukreyev, Lijuan Yang, Sherif R. Zaki, Wun-Ju Shieh, Pierre E. Rollin, Brian R. Murphy, Peter L. Collins, Anthony Sanchez
Journal of Virology Feb 2006, 80 (5) 2267-2279; DOI: 10.1128/JVI.80.5.2267-2279.2006
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KEYWORDS

Ebola Vaccines
ebolavirus
Hemorrhagic Fever, Ebola

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