The long road to developing an effective HIV vaccine has been fraught with false leads and disappointing outcomes, but promising preliminary results from a vaccine study conducted in South Africa and the United States suggest scientists may finally be on the right path.
The phase II study was designed to test for evidence that the vaccine could trigger an immune response - the body's natural defence against infection - and also that it would be safe.
According to Prof Gavin Churchyard of the Aurum Institute for Health Research, which conducted the South African arm of the trial, most participants who received the vaccine rather than a placebo demonstrated a strong immune response.
The results are sufficiently positive to support future trials investigating whether the vaccine can actually lower the likelihood of contracting HIV or, at the very least, slow the progression of HIV infection to AIDS.
"It's going to take us many more years to find an effective vaccine, but this is important news that we're on the right path," Churchyard told journalists at a briefing in Johannesburg on Friday, hosted by the South African AIDS Vaccine Initiative (SAAVI), a coordinating body for vaccine research funded mainly by the government.
In South Africa, 240 people at three different sites participated in the study, known as HVTN 204, which was sponsored by the US National Institutes of Health (NIH).
The vaccine was given in four doses: the first three contained genes from the three most prevalent strains of the HI virus - "the genes we want the body to mount an immune response to", explained Churchyard. The fourth injection contained a modified version of a virus called Adenovirus 5, which causes the common cold. The adenovirus acts as a "vector" to carry synthetic versions of HIV genes matching those in the three immunising shots.
Vaccines that can trigger an immune response are the new hope. According to Prof Lynn Morris, head of the HIV unit at the National Insitute of Communicable Diseases in South Africa, vaccines that help the body generate anti-bodies against HIV, the most commonly used method, have so far had disappointing results because of the HI viruses' ability to mutate rapidly.
"We don't know what type of immune response clears the virus, but we do know that a strong cellular immune response can control the virus," said Morris. "This type of vaccine is probably unlikely to prevent infection; it's more likely it will help control the virus in people who become infected."
Reducing the amount of virus in an HIV-infected person's system could have a significant indirect impact on the spread of the epidemic, added Dr Glenda Gray, of the University of the Witwatersrand Perinatal HIV Research Unit (PHRU), in Soweto. The lower someone's "viral load", the less likely they are to infect others.
While the main goal of most vaccines is preventative, Dr Efthyhia Vardas, also of the PHRU, presented preliminary findings from a trial of a therapeutic vaccine designed to help slow the progression of the virus in the estimated 40 million infected people worldwide.
HIV-positive trial participants who received this vaccine, developed by Finnish company FIT Biotech Plc, demonstrated significantly lower viral loads than those who received the placebo, but whether or not the effects would be long-lasting was not yet known, said Vardas.
The PHRU and the Aurum Institute are also recruiting 3,000 participants for a joint phase IIb HIV vaccine trial, the first of its kind in South Africa. The study will provide preliminary data on the efficacy of a vaccine known as HVTN 503, also designed to stimulate an immune response against HIV.
HVTN 503 will help researchers answer questions about the effect of gender on immune response, and whether a vaccine designed for sub-type B of the HI virus can protect people in Africa and other regions where sub-type C is most prevalent. Depending on the results, the next stage could be a much larger Phase III efficacy trial, the final stage before a vaccine could be manufactured and distributed.
"There's a whole pipeline of vaccines in development," said Churchyard, "and only a select few will make it into effectiveness trials."
South Africa is the only developing country involved in vaccine development but, according to Gray, a lack of local capacity to manufacture vaccines has prevented the country from becoming a "global player".
An international vaccine conference in Cape Town in 2008, when the annual meeting will be held outside of Europe and the United States for the first time, is likely to put the spotlight on South Africa's role in HIV vaccine research.