The Journal of Immunology, 2007, 178: 47.6.
Copyright © 2007 by The American Association of Immunologists, Inc.
Interferon mimetic as a therapeutic for lethal vaccinia virus infection
Chulbul M Ahmed,
James P Martin and
Howard M Johnson
Microbiology and Cell Science, University of Florida, 981 Museum Rd Rm 1052 PO Box 110700, Gainesville, FL, 32611-0700
Abstract
We have developed small peptide mimetics of gamma interferon (IFN
) that can bypass the poxvirus virulence factor B8R protein and can inhibit vaccinia virus replication in cell culture where intact IFN is ineffective. We demonstrate here that the mouse IFN mimetic peptide, IFN(95–132) with an attached lipophilic group for cell penetration, protects C57BL/6 mice against overwhelming lethal vaccinia virus infection. Intraperitoneal (IP) injection of mimetic before and at the time of intranasal (106 pfu) or IP (107 pfu) challenge with virus resulted in complete protection at 200 ug mimetic and 40 to 60 percent protection at 5 ug mimetic. Initiation of treatment of mice with IFN mimetic up to two days post infection resulted in complete protection against death, while initiation of treatment at six days post infection resulted in 40 percent protection. Administration of mimetic by the oral route also completely protected mice against the intranasal route of a lethal dose of vaccinia virus challenge. The mimetic also possessed adjuvant effects in boosting humoral and cellular immunity to vaccinia virus. The combination of antiviral and adjuvant effects by the IFN mimetic probably plays a role in its potent anti-vaccinia virus properties. These results suggest an effective therapeutic against ongoing, lethal poxvirus infections that taps into innate and adaptive host defenses.
Supported by NIH grant AI 056152 and DoD grant W911NF-05-1-0170, both to HMJ.
