1. ¹Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
2. ²Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
3. ³Department of Vaccine and Biologics Research, Merck Research Laboratories, West Point, PA 19486, USA

Correspondence: Richard E. Sutton, Fax: +1 713 798 3586. E-mail: rsutton@bcm.tmc.edu

Received 27 August 2005; Revised 6 February 2006; Accepted 23 February 2006.

Abstract

Here we describe as a potential vaccine candidate a replication-defective HIV that encodes multiple viral genes in addition to a cassette that includes both truncated cyclin T1 and an autofluorescent protein. After confirming functionality of the cyclin T1, we immunized mice intramuscularly once or twice with the replication-defective HIV vector pseudotyped with vesicular stomatitis virus (VSV) G protein (RD HIV), a plasmid encoding CMV-driven gag (gag DNA), or adenovirus gag (Ad5-gag). Capsid-specific antibody titers following RD HIV immunization were >10⁶/ml and approximately equivalent to those induced by gag DNA and Ad5-gag. Antibodies against the autofluorescent protein and VSV G were also detected. After RD HIV immunization ELISpot assays demonstrated Gag-specific interferon- (IFN-) SFU equivalent to that of Ad5-gag and fourfold greater than that of gag DNA. HIV polymerase-specific IFN- SFU values were similar, and boosting increased both antibody titers and the IFN- response. Challenge using vaccinia virus (VV)-gag demonstrated significantly lower recoverable VV for RD HIV-immunized mice compared to controls. No significant differences were observed in vaccinated mice challenged with wild-type VV. This study demonstrates the efficacy of RD HIV in conferring HIV-specific immunity and protection in mice and suggests its potential use in humans as either a prophylactic or a therapeutic vaccine.