16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

PRIME-BOOST VACCINATION WITH PLASMID DNA AND A CHIMERIC ADENOVIRUS TYPE 5 VECTOR WITH TYPE 35 FIBER INDUCES PROTECTIVE IMMUNITY AGAINST HIV

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAa0103

Xin K.-Q.¹, Someya K.², Yoshida A.¹, Honda M.², Okuda K.^1
1 Yokohama City University, Molecular Biodefense Research, Yokohama, Japan, ² National Institute of Infectious Diseases, AIDS Research Center, Tokyo, Japan

BACKGROUND: The replication-defective human Ad type 5 (Ad5) recombinants elicited the most potent CD8+ T cells responses and provided the high degree of protection in non-human primates. However, two major shortcoming of Ad5 vector are limited it for the clinical application. One of them is its high tropism for hepatocytes and the other is the pre-existing immunity against Ad5 in humans. 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.

METHODS: HIV Rev/gp160-expressing or Luciferase-expressing Ad5 vector and Ad5/35 vector were constructed. 1. Luciferase coding gene-containing Ad5 or Ad5/35 vector (10^11 vp/mouse) were injected intramuscularly (i.m.) into BALB/c mice. On days 3 and 10, distribution of Ad was imaged using a cooled in vivo imaging system (IVIS) CCD camera and analyzed. 2. BALB/c mice were primed with three i.m. injections of 100 ug of DNA vaccine and boosted with 10^10 vp of Ad5/35 vaccine. 3. Rhesus monkeys was i.m. immunized with 10^11 vp of Ad5/35 vaccine at weeks 0 and 8.

RESULTS: All of the Ad5/35-Luc vector remained at the injection site. In contrast, substantial amounts of the Ad5 vector migrated to the liver. 2. A single injection of Ad5/35 vaccine induced strong humoral and cell-mediated immunity in both mouse and monkey models. 3. The Ad5/35 vaccine was less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector.

CONCLUSIONS: These findings indicate that an Ad5/35 vector-based HIV vaccine may be of considerable value for clinical use.

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2006-08-13
ThAa0103

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