Efficacy and Mode of Action of Immune Response Modifying Compounds against Alphaviruses and Flaviviruses
Abstract
This study demonstrates that several immunomodulators protect mice against challenge with Semliki forest alphatogarvirus (SFV), Banzi flavivirus (BV), Caraparu bunyavirus (CV), and herpes simplex virus (HSV-2). Prophylactic treatment with maleic anhydride divinyl ether copolymer, C. parvum, CL246, 738, Ampligen, recombinant murine gamma interferon (rMuIFN-G) and recombinant human alpha A/D interferon (rHuIFN-A A/D) reduced mortality and increased survival time significantly. Early therapeutic treatment with some agents (CL246,3738, RMuIFN-G, rHuIFN-A A/D, and Ampligen) was also effective. Three pyrimidinones and various microbially derived compounds were found to have antiviral activity. Human recombinant alpha tumor necrosis factor (rHuTNF-A) and human macrophage colony stimulating factor (rHuCSF-M) were ineffective against the viruses tested. Among the active immunomodulators, broad spectrum antiviral activity was observed. There were differences in virus sensitivity with SFV and BV being the most sensitive and CV being the least sensitive to immunomodulator treatment. CV was most sensitive to treatment with the synthetic nucleoside analogue ribavirin. Many of the compounds activated macrophages and natural killer (NK) cell function. No unified immunomodulatory antiviral mechanism was identified. Selective depletion methods for M0 and NK cells were evaluated for potential use in assessing whether the antiviral activity of immunomodulators requires the presence of M0 or NK cell antiviral activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1987
- Accession Number
- ADA205252
Entities
People
- Angelo J. Pinto
- Margo Brinton
- Page S. Morahan