Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral

Authors: J. D. Gangemi; Abdul Ghaffar; Eugene P. Mayer; SOUTH CAROLINA UNIV COLUMBIA SCHOOL OF MEDICINE

Abstract:

Administration of multiple doses of Poly I:C-LC, Riker-3M or CL 246878 every other day for ten days did not prolong activation of immune functions. In some cases this treatment actually suppressed immune functions. Nevertheless, administration of multiple doses of these drugs had no adverse effect on resistance to Banzi virus infection. Encapsulation of Poly I:C in liposomes resulted in a formulation which was more effective than free drug in augmenting immune functions and resistance to virus challenge. Poly I:C conjugated to dextran was superior to free Poly I:C-LC in inducing interferon and stimulating the reticuloendothelial system. In addition, Poly I:C-dextran conjugates did not have the apparent toxic effects on the reticuloendothelial system that were observed with comparable doses of Poly I:C-LC. Type 2 dengue virus (strain 16681) infects squirrel monkeys as evidenced by both viremia and induction of anti-dengue antibodies. This virus model provides an opportunity to evaluate the therapeutic potential of immunomodulating and antiviral agents in non human primates infected with an arbovirus.

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APPROVED FOR PUBLIC RELEASE