African AIDS vaccines disappoint in trials
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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 Ini-
tiative (KAVI), in collaboration with researchers at the Univer-
sity 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 devel-
oped 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 elicit-
ing 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 immu-
nity 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 suc-
cessful.
The results have triggered a mixed response from those responsi-
ble for the trials. Andrew McMichael, director of the Human Im-
munology Unit of Britain's Medical Research Council the other
main sponsor admitted that the results s were disappointing.
But he said that he and his team were still keen to continue ex-
ploring the approach used in the vaccine design. "With a project
of this type you realistically have to expect to modify the vac-
cine as you go, and that it might be a second or third genera-
tion 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 vac-
cines 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 fa-
cilities 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 ques-
tions about the candidate vaccines "can be answered by the tri-
als that will be completed in Kenya and the United Kingdom".
Meanwhile McMichael says that, if IAVI funding for future devel-
opment of the two vaccines is withdrawn, his research team at
Oxford may seek other sources of financial support.