[NEW DELHI] Human trials of a US-made HIV vaccine will begin in India early next year, as earlier-announced trials of another vaccine, developed in India, face continued delays.
The delayed Indian vaccine uses six modified genes from the strain of HIV that circulates in most of India. The vaccine was developed by a team of Indian scientists, with support from the International AIDS Vaccine Initiative (IAVI). US-based pharmaceutical company Therion Biologics tested the vaccine in animals.
Plans to conduct 'phase I' safety trials of the Indian MVA in people were announced in 2003. The trials were to start in the first quarter of 2004, which was then delayed to the end of 2004. But the start date of the trials has still not been confirmed.
It uses a 'Modified Vaccinia Ankara' (MVA) virus (a version of the vaccine created to eradicate smallpox) as a means of carrying the modified HIV virus genes into the blood of the people vaccinated.
Officials at the National AIDS Research Institute (NARI) in Pune and National Institute of Cholera and Enteric Diseases in Kolkata, which designed and developed the vaccine, said they did not know when the trials would start.
Meanwhile, using an alternative approach — a 'recombinant Adeno Associated Virus' (rAAV) — the US company Targeted Genetics created a different vaccine, containing genes from the strain of HIV found in South Africa. It is this vaccine that will be tested in India soon, ahead of the MVA vaccine.
Sanjay Mehendale, deputy director at NARI, told SciDev.Net that the central ethics committee of the Indian Council of Medical Research and the Drugs Controller of India has approved the rAAV trial. He added that the vaccine will be tested in 30 people in India early next year.
"This is a part of the multi-national multi-centric study involving two sites each in Germany and Belgium in addition to the Pune site," he said.
The approval of trials of the foreign vaccine has raised questions over why the Indian vaccine has not yet received the green signal, and there are conflicting versions of its progress.
NARI's officer-in-charge Ramesh Paranjape says the organisation is awaiting information on the MVA vaccine from IAVI, while Sekhar Chakrabarti, the scientist at the National Institute of Cholera and Enteric Diseases who designed the Indian vaccine, says it seems the vaccine "is now on the shelf".
Informed sources told SciDev.Net the vaccine did not produce a sufficient immune response during pre-clinical tests. This May, an Indian newspaper quoted IAVI's medical director Jean-Louis Excler as saying there were "scientific hiccups" in the process.
Excler told SciDev.Net that pre-clinical tests showed the vaccine was safe and that it was able to provoke an immune response in animals, thus allowing for the preparation of clinical trials. He added that IAVI has started the process of applying for regulatory clearance to conduct the trials.
One concern with the rAAV vaccine to be tested in Pune is that it uses genes from a South African HIV strain whose ancestry differs from that of the Indian strain. But, says, Paranjape, the difference is unlikely to reduce its effectiveness in India because the African and Indian strains share a 90 per cent similarity in crucial parts of a gene inserted into the vaccine.
When tested in monkeys, the rAAV vaccine generated antibodies (proteins in the immune system that fight infection) to prevent infection of new cells, and white blood cells that kill any cells that are already infected. The immune responses lasted for up to one year. According to Paranjape, similarly promising results have emerged from research into mice.
A second Indian HIV vaccine, developed by Pradeep Seth's team at the All India Institute of Medical Sciences in New Delhi, is awaiting clearance for human trials. It is a DNA vaccine with an MVA vaccine as boost.
India has 5.1 million HIV infections, according to latest estimates from UNAIDS — the Joint United Nations Programme on HIV/AIDS - and is in urgent need of both vaccines and cheap antiretrovirals for HIV/AIDS.