SUMMARY: VIRxSYS Corporation's investigational HIV vaccine candidate, VRX1023 -- which uses a lentivirus vector in the same viral family as HIV -- produced a strong immune response and was associated with reduced viral load in SIV-infected macaque monkeys, researchers reported in an oral session at the 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010) last month in San Francisco.

By Liz Highleyman

Many HIV vaccines candidates use other viruses as "vectors" to carry HIV genes or antigens that stimulate an immune response. One common vector, adenovirus type 5 (Ad5; cause of the common cold), has demonstrated strong immunogenicity (ability to provoke an immune response), but has run into difficulties including pre-existing Ad5 immunity and other problems, leading to suboptimal efficacy, as seen in the large STEP trial.

Franck Lemiale from VIRxSYS and colleagues at the University of Pennsylvania School of Medicine looked at a different approach, using a lentivirus vector. The lentivirus ("slow virus") family includes retroviruses such as HIV itself and its simian equivalent SIV, but also many viruses not known to cause disease in humans.

Lentiviruses tend to be good at carrying genetic material into cells. The researchers therefore created a recombinant (genetically engineered) vaccine called VRX1023 consisting of a lentivirus vector carrying Gag, Pol, and Rev genes from SIV.

Macaque monkeys received injections of either the experimental vaccine or placebo, some of them after being "primed" with plasmid (free-standing) DNA. At 6 months after the last vaccine or placebo dose, the monkeys were "challenged" with a highly pathogenic strain of HIV.

The researchers monitored how many monkeys became infected and used a variety of laboratory assays to measure immune responses including T-cell activation, levels of cytokines, and production of antibodies against SIV and the lentivirus vector.

Results

	The VRX1023 vaccine did not prevent monkeys from becoming infected with SIV.
	However, vaccinated monkeys showed better control of the virus, as indicated by a 95% reduction in SIV viral load compared with non-vaccinated control animals.
	No adverse reactions were observed in any vaccinated animals after multiple vaccine doses.
	VRX1023 elicited immune responses, including SIV-specific CD8 T-cell responses and production of anti-SIV antibodies.
	T-cell responses were seen in monkeys that received the lentivirus vaccine with or without the DNA primer.
	Additional doses of the lentivirus vaccine did not increase production and neutralizing antibodies against the vector itself, suggesting it could be repeatedly administered without losing its effect.

"We are extremely encouraged by the results of this study," Lemiale said in a press release issued by VIRxSYS. "The combination of strong immune responses, viral control, and CD4 preservation is tremendous...It will be very interesting to see how it performs as a therapeutic vaccine in humans."

The company indicated that it is currently preparing an Investigational New Drug Application for the therapeutic use of the vaccine candidate in HIV positive patients.

VIRxSYS Corp, Gaithersburg, MD; University of Pennsylvania School of Medicine, Philadelphia, PA.

3/12/10

Reference
F Lemiale, M Morrow, L Shovlin, and others. Lentiviral Vector-based Anti-HIV-1 Vaccine Induces Strong T Cell and Antibody Responses in Macaques, with and without DNA Priming. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 81.

Other source
VIRxSYS. VIRxSYS Announces at CROI Promising Results from Its HIV Vaccine Study. Press release. February 18, 2010.