PHA-Exchange> African AIDS vaccines disappoint in trials

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From: "Vern Weitzel" <vern.weitzel at undp.org>

African AIDS vaccines disappoint in trials

Kimani Chege and David Dickson
3 September 2004
Source: SciDev.Net

Development work on a pair of possible AIDS vaccines that
had, until now, been widely seen as one of the most
promising ways of combating the disease may be abandoned
following disappointing results in clinical trials.

Two candidate vaccines, designed to be administered jointly,
have been developed by scientists in the Kenya Aids Vaccine
Initiative (KAVI), in collaboration with researchers at the
University of Nairobi and at the University of Oxford in the
United Kingdom.

The vaccines were designed after sex workers in a Nairobi
slum were found to possess immune systems that were able to
destroy the HIV virus. They are intended to stimulate the
same cell-mediated immune response in other individuals.

The vaccines — known as DNA.HIVA and MVA.HIVA — have been
developed as what is known as a 'prime-boost' pair. They are
intended to be given in combination, the DNA.HIVA being
administered first, and the MVA.HIVA — the 'boost' — second.
The hypothesis has been that a combination of the two may be
better at eliciting an immune response than one candidate
alone.

When the vaccine trials were launched in 2001, the head of
the International AIDS Vaccine Initiative, one of the
trials' main sponsors, described the approach they embodied
as "our best hope for ending the cycle of new HIV
infections".

But preliminary results of trials on 205 volunteers in
Kenya, Uganda and the United Kingdom, presented to a
conference in Lausanne, Switzerland, earlier this week,
showed that the immunity to HIV/AIDS was only boosted in
about one quarter.

This is far lower than the 60 per cent that IAVI requires to
judge a vaccine undergoing clinical trials to be considered
successful.

The results have triggered a mixed response from those
responsible for the trials. Andrew McMichael, director of
the Human Immunology Unit of Britain's Medical Research
Council — the other main sponsor — admitted that the results
were disappointing.

But he said that he and his team were still keen to continue
exploring the approach used in the vaccine design. "With a
project of this type you realistically have to expect to
modify the vaccine as you go, and that it might be a second
or third generation vaccine which actually ends up being
successful."

In contrast, the reaction from IAVI about future prospects
for the vaccine has been more negative. Indeed the
organisation has said that, if the final results of the
clinical results are no more promising, it will shift its
support to alternative vaccine designs.

In a statement, IAVI accepted that the trials had shown that
the vaccine was "generally safe and well tolerated". But it
added that the data "falls short of expectations" and that
the promise manifested in preclinical studies "has not held
up in humans."

"Unless there are new immune response data that are
dramatically different, IAVI will not develop the candidates
further, and will focus on its other research and
development projects," says Chrispin Kambili, head of IAVI's
Kenyan office.

The news about the poor results in the clinical trials has
been received with disappointment in Kenya by AIDS patients
who had hoped that the vaccine would prove to be an
effective way of combating the disease.

Others, however, argue that it is wrong to describe the
trials as a 'flop', as they have already produced a
significant amount of useful information. "At least we now
know that DNA-based vaccines are safe for human beings,"
Pamela Mandala, one of the first volunteers in the trials,
said in an interview with the East African Standard.

Despite the lack of success in the vaccine trials, Kenya
remains one of the few countries in sub Saharan Africa with
the capacity to undertake a HIV vaccine research due to
state-of-the-art facilities at KAVI.

So far, the vaccine trials have cost more than US$80
million.  As a result of the disappointing results, IAVI has
decided to cancel further clinical trials that were due to
take place in both Rwanda and the Netherlands, arguing that
remaining questions about the candidate vaccines "can be
answered by the trials that will be completed in Kenya and
the United Kingdom".

Meanwhile McMichael says that, if IAVI funding for future
development of the two vaccines is withdrawn, his research
team at Oxford may seek other sources of financial support.