Many STEPs away from an AIDS Vaccine

Many presentations dealt with the lessons learnt and trying to answer questions as to why the STEP trial failed and whether there needed to be a fundamental shift in focus.

The STEP trial was halted prematurely last year when analysis of the data suggested that that those who received the vaccine, which cannot cause HIV infection, might have an increased susceptibility to acquiring HIV and it was found that the Merck candidate vaccine neither prevented HIV infection nor lessened the amount of virus in those who became infected. One of the STEP trial arms, Phambili, was in its early stages in South Africa.

Further analysis has suggested that the circumcision or non-circumcision of some of the trial participants (most of the trial participants in the US arm were Men who have sex with Men) may explain why some were more susceptible to HIV infection.

Delivering the keynote address, Dr Anthony Fauci, Director of the US National Institute for Allergy and Infectious Diseases ‘€“ one of the key funders in the search for a vaccine – warned that the world may have to settle for a vaccine that was not 100% successful, but would make a major impact if used in combination with other prevention methods.

‘€œI wish we didn’€™t need an AIDS vaccine, but the need is as acute as ever,’€ said Dr Seth Berkley, President and founder of the International AIDS Vaccine Initiative (IAVI), a global not-for-profit organization involved in the search for a vaccine.

‘€œWomen still have no protection. There is no simple, easy method that women can use and for that reason it is critical that we continue to search for a vaccine. Yes, male circumcision reduces susceptibility, but it doesn’€™t protect the women. Treatment has also not had any significance on HIV incidence, so the search for a vaccine remains critical,’€ Berkley added.

Berkley admitted that following the STEP trial failure scientists had been forced to ‘€œtake a step back’€.

‘€œWe have outlined where the problems are and we understand we need to target this problem in a new way.’€

The first practical shift involves shifting resources away from the majority of vaccine candidates currently in the clinical pipeline on the basis of their probability of success, and steer freed resources into better candidate vaccines. A survey of more than 200 vaccine development projects revealed that on average only 20% advance from preclinical to Phase I trials.

This will see large-scale efficacy trials replaced by multiple and smaller preliminary efficacy trials, with only those candidates that show some evidence of efficacy advancing to large-scale trials.

Professor Bruce Walker of Harvard Medical School in the United States said that people who have been HIV positive for several years and have been healthy without having to use antiretrovirals, are helping scientists to better understand how to neutralize the virus.

‘€œThese people do eventually progress to a point where their CD4 cell count drops to below 350 (AIDS defining measure), but the majority are well for very long periods of time.

He said the only way to explain this was their body’€™s immune systems had figured out how to control the virus.

‘€œAmong these elite controllers (people who progress very slowly) HIV exhibited reduced replication capacity and there is definitely a suggestion of some immunological mechanism in these people. Something is done to the virus once it is inside these individuals,’€ Walker said.

Scientists were also looking at the use of live-attenuated viral vaccines (used for mumps, measles, rubella, oral polio, yellow fever and varicella), among the most effective vaccines available.

Live-attenuated simian immuno-deficiency virus (SIV), an HIV-like virus that infects and causes an AIDS-like disease in some species of monkeys, is offering scientists some clues and models as to what a future vaccine could be.

Research presented at the conference showed the macaque monkeys, infected with SIV and then given a vaccine, induced a hundred-fold reduction in the level of HIV infection. In some monkeys the level of the virus became undetectable.

However, no serious consideration is currently being given to developing a live-attenuated HIV vaccine because of concerns that the attenuated vaccine might revert to its virulent form and cause infection and disease.

Berkley, who has been part of the search for a vaccine since 1996, admits that it has not always been easy to keep spirits up. ‘€œI believe in the power of science and while I can’€™t guarantee a cheap, safe and efficacious vaccine, I know that immune protection is possible and that we will be able to translate it into something useable.

‘€œIf we had other powerful interventions at our disposal I wouldn’€™t feel so strongly. As long as there are practically zero interventions for women, the discovery of a vaccine needs to remain our number one priority,’€ said Berkley.

One could almost hear the collective sigh of relief at last week’€™s meeting.

For the first time since the International AIDS Conference hosted by Durban in July of 2000, science and the search for an improved response to the AIDS epidemic was not overshadowed and hijacked by inappropriate utterances by South Africa’€™s former President Thabo Mbeki or Health Minister Manto Tshabalala-Msimang.

Twenty days into her new job, South Africa’€™s new Health Minister Barbara Hogan used her first opportunity on a public platform to unequivocally declare that HIV caused AIDS and urged the almost 1 000 delegates to get on with the critical job of finding an AIDS vaccine.

Informing a round table meeting at the AIDS Vaccine Conference that his co-moderator Professor Helen Rees (Executive Director of the Reproductive Health Research Unit at Chris Hani Baragwanath Hospital) had unexpectedly been called to an urgent meeting with Hogan, Mitchell Warren of the AIDS Vaccine Advocacy Coalition quipped: ‘€œThis is the first time I have witnessed a South African researcher called to an urgent meeting with the South African Minister of Health and actually being excited by it.’€

‘€œIt is the dawn of a new age in South Africa,’€ said Berkley.

 ‘€œI have grown accustomed to South African researchers and scientists having to dodge the Minister and be careful about what they say. There is no doubt that they were affected (by the former Health Minister’€™s dissident stance), but it also produced heroes who doggedly continued with the job at hand,’€ said Berkley.

Berkley believes that the most destructive consequence of Tshabalala-Msimang’€™s disdain for science was the impact on young scientists considering a career in HIV/AIDS. He said that negative environment discouraged many young, aspiring scientists from ‘€œstepping up to the plate’€.

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