1. ¹Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, Yokohama, Japan
2. ²AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan
3. ³Department of Microbiology, Tokyo Dental College, Chiba, Japan
4. ⁴Laboratory of Gene Transfer and Regulation National Institute of Biomedical Innovation, Osaka, Japan
5. ⁵Department of Public Health, Yokohama City University, Graduate School of Medicine, Yokohama, Japan
6. ⁶Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD, USA

Correspondence: Dr K Okuda, Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

Received 3 April 2005; Accepted 18 June 2005; Published online 4 August 2005.

Abstract

Immunization involving a DNA vaccine prime followed by an adenovirus type 5 (Ad5) boost elicited a protective immune response against SHIV challenge in monkeys. However, the hepatocellular tropism of Ad5 limits the safety of this viral vector. This study examines the safety and immunogenicity of a replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35) in BALB/c mice and rhesus monkeys. This novel Ad5/35 vector showed minimal hepatotoxicity after intramuscular administration with the novel Ad5/35 vector. In addition, an Ad5/35 vector expressing HIV Env gp160 protein (Ad5/35-HIV) generated strong HIV-specific immune responses in both animal models. Priming with a DNA vaccine followed by Ad5/35-HIV boosting yielded protection against a gp160-expressing vaccinia virus challenge in BALB/c mice. The Ad5/35-HIV vector was significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector. These findings indicate that an Ad5/35 vector-based HIV vaccine may be of considerable value for clinical use.