Immunoprophylaxis of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with recombinant Eimeria profilin-like antigen.
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-gamma and TNF-alpha were assessed to evaluate the induction of these inflammatory mediators known to be induced in mice following exposure to rEA. A dose of 100 microg 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-gamma 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.
Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA. bgowen@cc.usu.edu
Brian B
BB
Gowen
John W
JW
Judge
Min-Hui
MH
Wong
Kie-Hoon
KH
Jung
Charles F
CF
Aylsworth
Peter C
PC
Melby
Barnett
B
Rosenberg
John D
JD
Morrey
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D002044:Bunyaviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D006224:Cricetinae; D004539:Eimeria / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D020382:Interleukin-18 / Q000008:administration & dosage / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology; D008647:Mesocricetus; D016856:Phlebovirus / Q000276:immunology*; D000091402:Prohibitins; D011994:Recombinant Proteins / Q000276:immunology; D014158:Transcription, Genetic
D000953:Antigens, Protozoan; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D007376:Interleukin-2; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011994:Recombinant Proteins; D007371:Interferon-gamma