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Journal of Virology, February 2008, p. 1332-1338, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01822-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus{triangledown}

Jay W. Hooper,* Anthony M. Ferro, and Victoria Wahl-Jensen

U.S. Army Medical Research Institute of Infectious Diseases, Virology Division, 1425 Porter Street, Fort Detrick, Maryland 21702

Received 20 August 2007/ Accepted 8 November 2007

Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD50], ~100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days –1 and +5 relative to challenge were protected against intranasal challenge (21 LD50). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.

* Corresponding author. Mailing address: Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702. Phone: (301) 619-4101. Fax: (301) 619-2439. E-mail: jay.hooper{at}amedd.army.mil

{triangledown} Published ahead of print on 21 November 2007.

Journal of Virology, February 2008, p. 1332-1338, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01822-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Safronetz, D., Hegde, N. R., Ebihara, H., Denton, M., Kobinger, G. P., St. Jeor, S., Feldmann, H., Johnson, D. C. (2009). Adenovirus Vectors Expressing Hantavirus Proteins Protect Hamsters against Lethal Challenge with Andes Virus. J. Virol. 83: 7285-7295 [Abstract] [Full Text]  


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