A T-cell infected with HIV (Image: LBN)

Almost 26 years after HIV was discovered to be the cause of AIDS, a vaccine has at last shown signs of protecting people. Results of the RV144 trial on 16,000 volunteers in Thailand show that those receiving the vaccine reduced their risk of HIV infection by about a third – the first evidence that a vaccine might work. The two largest previous vaccine trials, in 2003 and 2007, failed, and that had researchers wondering if there would ever be an effective vaccine.

So is this result – announced on Thursday by the US National Institutes of Health, which funded the trial – the momentous breakthrough we’ve been waiting for, or are the results too modest to get excited about? New Scientist takes a look.

How excited should we be?


It is extremely encouraging that, at last, a vaccine has shown signs of providing protection. The reduction in risk of infection is not huge – 31 per cent: male circumcision reduces the risk of infection by double that, for comparison. The real significance is that there was any measurable effect at all after researchers had begun to lose hope that a vaccine would ever work.

Why did they think a vaccine would never work?

HIV continually mutates and evolves, so even if someone had been vaccinated against earlier variants, subsequent mutants may go unnoticed, multiply and overwhelm the immune system.

Also, HIV is unusual in that it attacks the very white cells that are meant to fight disease. One fear from the earlier “STEP” vaccine trial – now dispelled – was that by stimulating the immune system, vaccines simply generate extra white blood cells for HIV to infect, making the situation worse. To the relief of vaccine researchers, more recent investigations showed this wasn’t what happened, reviving hopes for vaccines generally.

How powerful is the new vaccine?

The figures indicate only a slender protective benefit (PDF). Of 8197 vaccinated volunteers, 51 became infected, compared with 74 of the 8198 who received a dummy vaccine.

The investigators say that the 31 per cent reduction risk is statistically significant, however, meaning that it was probably down to the vaccine – not other, random factors that raised protection in the treated group, such as better self-protection with condoms and avoiding unsafe sex generally.

Do they know yet how it protected people?

No. The next step is to find out by analysing samples from volunteers. One slightly worrying finding is that people who did become infected had similar levels of virus in their blood whether or not they’d been vaccinated. This suggests that if vaccinated people do get infected, their immune systems still struggle to combat the virus. Subsequent investigations by the researchers should reveal what effect, if any, the vaccine had on people’s immune systems.

How was the vaccine meant to work?

The vaccine was a combination of two separate components. The first, called Alvac, is a harmless form of the virus that causes canarypox loaded with genes that make three key HIV proteins: env, gag and pol. The hope is that the immune system produces white blood cells which recognise these viral proteins in a real infection and make antibodies to combat HIV. As well as four shots of Alvac, volunteers received two booster shots of the second component, Aidsvax, a genetically engineered version of the gp120 protein found on the surface of HIV.

Was the vaccine safe?

Yes. No side effects.

When did the trials start, and who organised them?

The trials began in 2003 and ended in 2006, and were run by the Thai Ministry of Public Health in collaboration with the US Military HIV Research Program, based in Rockville, Maryland. The trial was paid for by the office of the US army Surgeon General, with logistical and research support from the NIH. The main vaccine, Alvac, was produced by Sanofi Pasteur, the French-based pharmaceutical giant, and Aidsvax by Genentech of the US. Ironically, Aidsvax used alone was one of the earlier vaccine failures.

What happens next?

The researchers will analyse the results in detail to assess how the vaccine worked, if at all: the results will have to be peer-reviewed and published to convince other AIDS researchers that the effects were genuine. The investigators will also need to assess how many HIV strains the vaccine will protect against – it was designed against the subtype B and E strains of HIV common in Thailand, although B is also the commonest in the US.

Clearly a vaccine is still some time away, and this one may only be effective against a limited number of strains.

Indeed. We don’t know exactly how the vaccine performed, and whether other factors may have played a part in the result. For example, how much of the difference in infection rates was simply down to chance? And a big worry about any vaccine is that it will encourage recipients to mistakenly think they’re immune, so they engage in riskier sex.

So, a vaccine’s some time off. What do we do in the meantime?

There are other types of treatment and protection under investigation. Antiretroviral drug treatment (ART) already provides excellent protection to those who receive it, virtually eliminating the virus from the body. The problem has been making sure that all infected individuals receive ART, especially in Africa.

One proposal that has great potential but is very expensive is to give people ART as soon as possible after they’ve been infected, instead of waiting until the concentrations in their blood of the CD4 cells targeted by HIV fall below a pre-selected threshold. Backers of the “instant treatment” approach say that it would eliminate the virus from circulation far faster, reducing the opportunities for infected people to infect others. ART could even be taken prophylactively, before infection.

Any other promising treatments?

One of the most encouraging approaches is to try to stop the virus getting into white blood cells via a molecule on the surface called CCR5. If cells lack this molecule, the virus can’t invade them. So some companies are developing drugs and treatments based either on blocking CCR5 with drugs or eliminating it from people’s white blood cells through gene therapy, effectively rebuilding people’s immune systems from scratch so that HIV can’t invade their cells.

Another novel gene-therapy approach tried recently is to inject muscles with viruses carrying genes for antibodies that are especially potent against HIV.

So can we beat HIV?

Probably, but it’s an open question how long it takes to produce a “universal” vaccine that works against all strains of HIV.

Even aside from today’s encouraging result, there are other rays of hope. One recent breakthrough was the discovery of an extremely vulnerable region of the HIV virus, providing a target for new and far more effective vaccines.

But it will take years and lots of research to get there. In the meantime, the virus marches on. Every day, 7000 people become infected, and thousands more lack the ART drugs they need to survive, especially in sub-Saharan Africa.