This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Safronetz, D.
Right arrow Articles by Johnson, D. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Safronetz, D.
Right arrow Articles by Johnson, D. C.

 Previous Article  |  Next Article 

Journal of Virology, July 2009, p. 7285-7295, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00373-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Adenovirus Vectors Expressing Hantavirus Proteins Protect Hamsters against Lethal Challenge with Andes Virus {triangledown}

David Safronetz,1,2,{dagger} Nagendra R. Hegde,3,{ddagger} Hideki Ebihara,2,4,{dagger} Michael Denton,3 Gary P. Kobinger,1,2 Stephen St. Jeor,5 Heinz Feldmann,1,2,{dagger} and David C. Johnson3*

Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3,1 Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada R3E 3R2,2 Department of Molecular Microbiology & Immunology, Oregon Health & Sciences University, Portland, Oregon 97219,3 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan,4 Department of Microbiology & Immunology, University of Nevada, Reno, Nevada 895575

Received 19 February 2009/ Accepted 23 April 2009

Hantaviruses infect humans following aerosolization from rodent feces and urine, producing hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Due to the high rates of mortality and lack of therapies, vaccines are urgently needed. Nonreplicating adenovirus (Ad) vectors that express Andes hantavirus (ANDV) nucleocapsid protein (AdN) or glycoproteins (AdGN and AdGC) were constructed. Ad vectors were tested for their ability to protect Syrian hamsters from a lethal ANDV infection that mimics the pulmonary disease seen in humans. When administered once, all three Ad vectors, individually or in combination, elicited a robust immune response that protected hamsters. No vaccinated animal died, and there were no obvious clinical signs of disease. Further, hantavirus RNA was not detected by sensitive reverse transcription-PCR in tissues and blood of hamsters immunized with both AdGN and AdGC. Cellular immunity appeared to be important for protection because the AdN vector completely protected animals. All three Ad vectors produced strong cytotoxic T-lymphocyte responses directed to hantavirus proteins in mice. Moreover, hamsters vaccinated with AdN, AdGN, or AdGC produced no detectable neutralizing antibodies yet were protected. These Ad vectors represent the first vaccines that prevent lethal hantavirus disease and, in some instances (AdGN and AdGC), provide sterile immunity. These observations set the stage for a more detailed characterization of the types of immunity required to protect humans from hantavirus infections.

* Corresponding author. Mailing address: L-220, Basic Sciences Bldg., Oregon Health & Sciences University, Portland, OR 97239. Phone: (503) 720-4854. Fax: (503) 494-6862. E-mail: johnsoda{at}ohsu.edu

{triangledown} Published ahead of print on 29 April 2009.

{dagger} Present address: Laboratory of Virology, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.

{ddagger} Present address: Bharat Biotech Foundation, Genome Valley, Shameerpet, Hyderabad 500 078, India.

Journal of Virology, July 2009, p. 7285-7295, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00373-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»