Promising Data Regarding DermaVir for Therapeutic Vaccine

By Brian Boyle, MD

There is a pressing need for simple and effective treatment strategies for HIV infection that result in long-term virologic control and avoidance of toxicities. Many novel therapeutic approaches are being explored.

One approach is in "leveraging the immune system" since boosting HIV-specific immune responses in chronic infection may offer a potential for synergy with antiretroviral drugs, enhancing durable control of viral replication.

In a study presented at the 6th International Congress on Drug Therapy in HIV Infection data regarding a novel immunotherapeutic, DermaVir, was presented. DermaVir delivers a replication and integration defective SIV/HIV DNA to dendritic cells after topical skin application. Unlike other vaccine technologies, DermaVir is designed to transduce Langerhans cells on the surface of the skin, which are "professional" presenting cells that stimulate CD4, CTL and naïve CD4 cell growth. Once the SIV/HIV DNA is present in the Langerhans cells, they which then migrate to the lymph node and mature to antigen-expressing dendritic cells, and elicit SIV/HIV-specific T cell immunity.

In several animal studies, the therapeutic effect of DermaVir was evaluated in chronically SIV251-infected rhesus macaques that were randomized to receive intermittent structured treatment interruptions (STI) and highly active antiretroviral therapy (HAART) (3 weeks on HAART & 3 weeks off) with or without DermaVir.

The investigators found monkeys that received DermaVir had excellent suppression of HIV replication during the STI periods, while those who did not receive DermaVir had very little, if any, virologic control during the STIs. The control of viral load during the STI in the DermaVir treated monkeys was associated with augmented SIV-specific CD8 and CD4 T cells. In these studies, DermaVir therapy did not show signs of toxic side effects.

Based upon these data, the presenter concluded that "The antiviral potency, topical application and infrequent dosing schedule make DermaVir a very attractive treatment option for HIV-infected individuals. Complementing the therapeutic efficacy of HAART with DermaVir immunotherapy could prolong the effectiveness of antiretroviral drugs and thereby delay development of drug resistance."

Phase I human studies using DermaVir will begin shortly.

11/22/02

Reference
J Lisziewicz and others. DermaVir: a new topical DNA vaccine for the treatment of HIV/AIDS. Plenary Session 7.2. 6th International Congress on Drug Therapy in HIV Infection. November 17-21, 2002. Glasgow, UK.