Glaxo to begin trials of HIV vaccine in humans
(02/01/2002) (Agencies)

British drugmaker GlaxoSmithKline Plc on Thursday said it will begin human trials in the United States this year on a vaccine to prevent infection with HIV, the virus that causes AIDS.

Healthy males and females who have not been exposed to the virus and who are at low risk of HIV infection will be enrolled later this year for the trials which will take place at up to 11 clinical research centers in the United States, the firm said.

The vaccine, developed by the drug giant's GlaxoSmithKline Biologicals vaccine unit, consists of several proteins in and on the outside of the virus as well as an "adjuvant" substance meant to enhance the effectiveness of the vaccine.

In pre-clinical trials, the experimental vaccine protected rhesus monkeys from simian-human immunodeficiency virus (SHIV), a potent virus similar to HIV, Glaxo said.

"The direct relevance of these animal studies to humans is not known. Human data can be obtained only from human studies," Glaxo cautioned. The US trials represent the first time that the Glaxo vaccine has been tested on humans.

Monkeys given the Glaxo vaccine maintained their levels of key immune-system blood cells, called CD4 cells, that help the body fight off bacteria and viruses. HIV works by invading the body, taking refuge in such CD4 cells and reproducing inside them like wildfire.

But more and more CD4 cells are killed in the process, leaving the immune system prey to deadly opportunistic infections that would not affect people with healthy immune systems.

Glaxo said the vaccine would be aimed at preventing infection with at least two of the most prevalent strains of HIV, found in both the developed and developing world.

The trials will be conducted in collaboration with the HIV Vaccine Trials Network (HVTN), which was created in 1999 by the National Institute of Allergy and Infectious Diseases to promote development of HIV vaccines.

15-MONTH TRIAL

The Phase I trial is designed primarily to test for safety, not for effectiveness. In such safety trials low-risk people are tested, with higher-risk populations tested in later Phase II and III efficacy trials.

Glaxo's vaccine will contain traces of two proteins, called Nef and Tat, that the virus needs to replicate. It also contains bits of a protein called gp 120 that is found on the shell, or envelope, of the virus.

"This is the first time that the Nef and Tat proteins have been stuffed into the same vaccine. It's a novel approach," said Dr. Thomas Evans, a professor of medicine at the University of California-Davis that is leading the US trials.

"We had to include the adjuvant and all three proteins -- Nef, Tat and gp 120 -- to protect the monkeys," Evans said in an interview. He added the adjuvant was made from a variety of refined substances, including one derived from the bark of a tree.

The safety trial will enroll 84 people over a 15-month period, some of whom will receive the vaccine and others who will receive dummy vaccines.

If the Glaxo vaccine looks promising and safe, Evans said it would be tested in big later-stage trials that could take another two to four years to complete.

US drug giant Merck & Co. Inc is also in the early stages of testing an HIV vaccine in people, and has predicted it will prove successful within the next decade.

About 36 million people worldwide are infected with HIV, with another 15,000 being infected every day, according to estimates of the World Health Organization.

Although expensive cocktails of anti-HIV drugs can control the virus and stave off dangerous infections, the fast-mutating virus quickly can become resistant to the medicines and render them ineffective for many patients.

Health officials have said the only real hope, and affordable means, of containing the HIV epidemic is a preventive vaccine.