Stalking the AIDS vaccine: Patience required

By Pat Reber Jun 10, 2011, 0:30 GMT

US senator John McCain (L) greets Phyu Phyu Thin(R) member of the National League for Democracy party(NLD) and leader of the private HIV/AIDS care center which is run by the members of the National League for Democracy party(NLD) at the south Dagon Township, Yangon,Myanmar, 2 June 2011. McCain is part of a US delegation in the country to determine whether the country\'s new military-backed government is serious about pursuing economic and political reforms. EPA/NYEIN CHAN NAING

Washington - In the hunt for an HIV/AIDS vaccine, there is hope and disappointment around every corner.

The dreaded immune deficiency disease turns 30 this month as the pandemic's death toll also reached a ghoulishly round number: 30 million gone in 30 years.

'Yet the story of HIV is not one of loss alone,' researchers at the International AIDS Vaccine Initiative (IAVI), which raises money and works with a world network of investigators, insisted earlier this month.

The promise seems mighty thin indeed: In 15 years, the New York-based IAVI and its partners have developed 17 vaccine candidates, nine of which entered human trials in 11 countries. None has yet panned out.

The US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, which administers the lion's share of the world's estimated 850 million dollars spent on vaccine research every year, has repeatedly raised hopes with vaccine candidates only to have them dashed, as happened with one called PAVE in 2008.

A broad battery of medicines has been developed to hold HIV/AIDS in check and extend lifetimes for people who can afford them, but the drugs will 'never beat the pandemic,' wrote IAVI's Seth Berkeley and Phill Wilson of the Black AIDS Institute.

Only a vaccine can do that - one which can head off the tricky Human Immunodeficiency Virus (HIV) as it enters the body and before it starts playing a shape-shifting game of hide and seek with the immune system.

In the past three years, however, since NIAD's director Anthony Fauci gave a sobering reality check in 2008 and called for a return to basic research, vaccine researchers have gotten new impetus.

The biggest step came in Thailand in 2009, where US military and Thai researchers found that an AIDS vaccine candidate, RV144, reduced the risk of infection by 31 per cent. A total of 16,000 volunteers participated in the controversial trial, which combined two vaccines that had previously proved ineffective - Alvac-HIV and Aidsvax.

While modest in its results, it was the first demonstration that a vaccine can protect people from HIV, experts said. Two repeat RV144 clinical trials are planned, one for Thailand and another for southern Africa, using segments of the respective regional varieties of HIV virus in the vaccine.

'People are now saying, 'It's not a question of if, but a question of when,'' IAVI's Chief Operating Officer David Cook told the German Press Agency, dpa.

The traditional approach to vaccines - using live virus to induce antibodies and thus immunity without causing illness - has not worked with HIV because the virus has an astonishing ability to change and disguise itself from the body's defenses.

The virus constantly changes its surface proteins to evade detection, resulting in a very large number of HIV variants worldwide.

That's why some of the focus of recent research has also been on isolating the antibodies themselves that can neutralize a broad spectrum of HIV variants. Two such proteins - called VRC01 and VRC02 - were isolated just last year, with the ability to neutralize more than 90 per cent of known global HIV strains.

A crucial step is figuring out how best to deliver the HIV vaccine into the human body. The 2009 Thai vaccine for example used a canary pox virus that normally causes disease in birds but not humans.

But many of these transport vehicles, or vectors, soon lose their effect, or provoke the body's defences too late, by which time it's 'basically game over,' said Louis Picker, a physician researcher at Oregon Health & Science University.

Picker and his team, which included IAVI, set out to find a vector that would stay in the body for a long time, and came up with a form of the herpes virus (not herpes simplex) called cytomegalovirus (CMV).

In a 10-year project, they tested their idea on rhesus maqaque monkeys using monkey forms of HIV, called SIV, and of CMV. After exposure to a 'highly pathogenic and aggressive' SIV, especially concentrated for the test, 13 of 24 monkeys became infected but managed to keep the virus from multiplying, researchers reported in May.

Twelve of the 13 were virtually virus free after more than a year, a development that IAVI's Cook called 'the most profound protection we've seen in an experimental vaccine.'

The key was the herpes vector. The human form of this herpes virus is found in about 98 per cent of people in the developing world and about 60 per cent of people in the developed world, Picker said.

In its natural form, it causes few discernible effects, but serves to provoke its own immune reaction to keep it in check - and also fights off many other illnesses, keeping much of the human population healthy.

By adding the virulent SIV to the herpes virus, it was like picking a fight with 'the toughest team on the block ... and seeing what their vulnerabilities were.'

The herpes virus 'fools the body into thinking it's always under threat, and keeps the soldiers ready at the point where ... the (HIV/SIV) virus comes into the body,' Picker said.

'The idea is, you can stop it at the beaches,' Picker said.

The next step will be adapting the vaccine for human use.

Picker compares the challenge of finding a vaccine to a 'very high, seemingly unscalable cliff and so far efforts to climb it have not reached the top.'

'What this work does is basically show a path to the top. We still have to put on our climbing gear and climb the path,' he said.

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