This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ajariyakhajorn, C. Articles by Libraty, D. H. Search for Related Content PubMed PubMed Citation Articles by Ajariyakhajorn, C. Articles by Libraty, D. H.

Randomized, Placebo-Controlled Trial of Nonpegylated and Pegylated Forms of Recombinant Human Alpha Interferon 2a for Suppression of Dengue Virus Viremia in Rhesus Monkeys

United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand,¹ Walter Reed Army Institute of Research, Washington, D.C.,² Queen Sirikit National Institute of Child Health, Bangkok, Thailand,³ Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts⁴

Received 6 June 2005/ Returned for modification 15 July 2005/ Accepted 16 August 2005

Dengue fever and dengue hemorrhagic fever are caused by infection with any one of the four dengue viruses (DVs) and are significant public health burdens throughout the tropics. Higher viremia levels are associated with greater dengue disease severity. A therapeutic intervention to suppress viremia early in DV infection could potentially ameliorate severe disease. Recombinant alpha interferon 2a (rIFN--2a, Roferon-A) suppressed DV replication in human peripheral blood mononuclear cells in vitro. We therefore examined the effects of rIFN--2a and pegylated recombinant IFN--2a (PEG-rIFN--2a, PEGASYS) on DV serotype 2 (DV-2) viremia in rhesus monkeys. Flavivirus-naïve monkeys were inoculated with DV-2 and randomized to receive a single dose of rIFN--2a (10 million international units/m²) versus placebo or PEG-rIFN--2a (6 µg/kg) versus placebo 1 day after the onset of viremia. Serial daily viremia levels were measured, and convalescent-phase DV-2 neutralizing antibody titers were determined. Compared to placebo, a single injection of rIFN--2a temporarily suppressed DV-2 replication and delayed the time to peak viremia by a median of 3 days. However, measures of total viral burden were not different between the two groups. A single injection of PEG-rIFN--2a significantly lowered daily viremia levels and improved virus clearance, starting 48 h after administration. There were no significant differences in DV-2 neutralizing antibody titers between the treatment and placebo groups at 30 and 90 days postinfection. Based on their individual effects, future studies should investigate a combination of rIFN--2a and PEG-rIFN--2a for suppression of dengue virus viremia and as a potential therapeutic intervention.