Immunoprophylaxis of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with recombinant Eimeria profilin-like antigen

Brian B. Gowen, John W. Judge, Min Hui Wong, Kie Hoon Jung, Charles F. Aylsworth, Peter Melby, Barnett Rosenberg, John D. Morrey

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Recombinant Eimeria antigen (rEA) has been shown to have potent anticancer and antiviral activity in respective mouse disease models, presumably through robust immune stimulation that occurs via TLR11, a pattern recognition receptor that recognizes profilin-like proteins expressed on apicomplexan protozoans. Comparable immunostimulatory activity in other species has yet to be demonstrated. Since rEA is known to be highly effective in treating Punta Toro virus (PTV) infection in mice, its ability to elicit protective immunity in the hamster PTV infection model was investigated. rEA was given alone, or in combination with IL-18 or IL-2, and virally challenged hamsters were observed for mortality. Cytokine transcript profiles for IL-12p40, IL-21, IFN-γ and TNF-α were assessed to evaluate the induction of these inflammatory mediators known to be induced in mice following exposure to rEA. A dose of 100 μg of rEA, given once 4 h prior to viral challenge, and a second time on day 3 of the infection, was found to be the most effective prophylactic therapy protecting 60% of treated hamsters from mortality, compared to only 5-10% observed in animals receiving placebo. Increased expression of IFN-γ and IL-12p40 was evident following treatment with rEA. The data suggest that rEA does induce host antiviral responses in hamsters that result in significant protection from death, although determining the most appropriate dose for intervention in other species, including humans, will likely be challenging.

Original languageEnglish (US)
Pages (from-to)1089-1094
Number of pages6
JournalInternational Immunopharmacology
Volume8
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Bunyaviridae Infections
Phlebovirus
Profilins
Eimeria
Cricetinae
Viruses
Antigens
Interleukin-12 Subunit p40
Virus Diseases
Antiviral Agents
Pattern Recognition Receptors
Interleukin-18
Mortality
Interleukin-2
Immunity
Placebos
Cytokines

Keywords

  • Antiviral
  • Immune modulator
  • Phlebovirus
  • Profilin
  • Punta Toro virus

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Immunoprophylaxis of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with recombinant Eimeria profilin-like antigen. / Gowen, Brian B.; Judge, John W.; Wong, Min Hui; Jung, Kie Hoon; Aylsworth, Charles F.; Melby, Peter; Rosenberg, Barnett; Morrey, John D.

In: International Immunopharmacology, Vol. 8, No. 8, 08.2008, p. 1089-1094.

Research output: Contribution to journalArticle

Gowen, Brian B. ; Judge, John W. ; Wong, Min Hui ; Jung, Kie Hoon ; Aylsworth, Charles F. ; Melby, Peter ; Rosenberg, Barnett ; Morrey, John D. / Immunoprophylaxis of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with recombinant Eimeria profilin-like antigen. In: International Immunopharmacology. 2008 ; Vol. 8, No. 8. pp. 1089-1094.
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