Vical Incorporated has announced the initiation of a National Institutes of Health (NIH) sponsored phase 1 clinical trial of a "prime-boost" vaccine approach designed to prevent or control disease in patients already infected with HIV.

The trial involves priming an immune response with multiple doses of a plasmid DNA vaccine, based on Vical's proprietary DNA delivery technology, and boosting the response with a single dose of adenoviral vector vaccine given at a later date.

The vaccine was developed by scientists at the Dale and Betty Bumpers Vaccine Research Centre (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, and was manufactured by Vical. The vaccine incorporates HIV genetic material from the three most globally important HIV subtypes, clades A, B and C, which are involved in about 85 per cent of all HIV infections around the world. The same vaccine is currently being tested in a preventive setting through a multinational phase 2 trial initiated in October 2005. Results from a phase 1 trial in HIV-uninfected subjects showed that the prime-boost approach was well tolerated and effective in producing potent cellular and antibody immune responses, including specific responses against each of the HIV subtypes. The new phase 1 trial is the first therapeutic application of a "prime/boost" vaccine against HIV in the VRC programme.

"Antiviral drugs have dramatically improved the outlook for HIV-infected individuals," said Vijay B. Samant, Vical's President and CEO, "but complicated treatment regimens, serious side effects and increasing drug resistance call for better long-term solutions. A post-infection vaccine that would allow the immune system to suppress viral loads could provide significant benefits both to prevent disease symptoms in the individual and potentially to reduce disease transmission between individuals. We are excited that our collaborators at the VRC have advanced into human testing with this novel vaccine application."

The vaccine used in the phase 1 trial incorporates parts of four HIV genes. Three of these vaccine components are modified versions of HIV genes called gag, pol and nef, synthetically made based on sequence from clade B, the subtype that predominates in Europe and North America. The fourth vaccine component is a modified version of the HIV gene named env. The env gene codes for a protein on the outer coat of the virus that allows it to recognize and attach to human cells. VRC scientists were the first to combine modified env from clades A and C, which are the most common in Africa and parts of Asia, with the modified env gene from clade B. The study is being conducted at the NIH Clinical Centre. The trial is double-blinded and placebo-controlled, and will evaluate safety, tolerability and immune response. Subjects will continue highly active antiretroviral therapy (HAART) throughout the trial.

Vical has produced multiple DNA vaccines for the VRC against infectious disease targets including Ebola, severe acute respiratory syndrome (SARS), and West Nile virus, all of which have advanced into phase 1 clinical trials over the past three years.