Adenovirus vectors expressing hantavirus proteins protect hamsters against lethal challenge with Andes virus

David Safronetz, Nagendra R. Hegde, Hideki Ebihara, Michael Denton, Gary P. Kobinger, Stephen St. Jeor, Heinz Feldmann, David C. Johnson

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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 AdG N 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.

Original languageEnglish (US)
Pages (from-to)7285-7295
Number of pages11
JournalJournal of virology
Volume83
Issue number14
DOIs
StatePublished - Jul 1 2009

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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. Journal of virology, 83(14), 7285-7295. https://doi.org/10.1128/JVI.00373-09