The Tuberculosis Research Centre (TRC) Chennai is planning to conduct the phase I trial of prime-boost HIV vaccine in early next year. The US-based International AIDS Vaccine Initiative (IAVI) in association with ICMR and NACO is spearheading the initiative, said Dr V D.Ramanathan, deputy director and principal investigator at the TRC.

ADVAX, a DNA-based vaccine, which has been tested in the United States, will be used as the prime, and the MVA-based vaccine, which was tested during the phase I trial at the TRC, will be the boost. Along with this, a separate phase I prime-boost vaccine trial using ADVAX and MVA will be conducted in London.

ADVAX contains a few HIV genes, while MVA is a vector that contains six HIV genes. The Genetic Engineering Approval Committee (GEAC) has to approve the import of the vaccine and the Drugs Controller General of India (DCGI) has to accord the necessary permission before the trial can be conducted in India.

Earlier, the TRC had successfully conducted phase 1 trials of an MVA-based AIDS vaccine candidate (TBC-M4), which indicated that the vaccine candidate had acceptable levels of safety and was well tolerated. The trial was conducted under the aegis of an MoU between the Government of India-through ICMR, NACO and IAVI. The TRC's research activities are complementing the National Tuberculosis Control Programme. For improving the immune response, this vaccine (TBC-M4) will be used in combination with other candidate AIDS vaccines (ADVAX).

The prime-boost strategy is expected to improve the immune response and hence make the vaccine more efficacious. " Prime-boost (PB) is to stimulate the immune response multiple number of times. For this, the same vaccine may be used as in the recently concluded MVA trial in the TRC where it was given 3 times. However, what PB usually means is that two different vaccines are given at different times and this is known as heterologous PB", Dr Ramanathan said.

The vaccine candidate, TBC-M4, is based on a vector built from recombinant Modified Vaccinia Ankara (MVA). It was designed by a biotech firm in the US in collaboration with the National Institute of Cholera and Enteric Diseases (NICED). It targets HIV-1 subtype C, the most predominant HIV subtype in India, Dr Ramanathan told Pharmabiz.

The phase 1 clinical trial of TBC M4 was initiated in January 2006 and was completed in February 2008. But he said currently the MVA- based vaccine would not be taken forward to phase II because the Centre wanted to improve the immune response before going further. But unlike the two vaccine trials, the trial now being planned will be a prime-boost vaccine, he said.

Regarding the phase 1 trials, the scientist at the TRC said the proportion of volunteers whose immune systems responded to the vaccine candidate suggests the candidate holds promise. The trial was done using two doses of the candidate vaccine. After three injections, 82 per cent of the volunteers who received a low dose and 100 per cent of those who received a high dose registered immune responses to the vaccine. The 100 per cent response rate is greater than that seen with the majority of AIDS vaccine candidates tested in humans to date. However the strength and diversity of these immune responses were modest. It may be possible to boost the immune response, if this vaccine is used in combination with other candidate AIDS vaccines.

Dr.Ramanathan said the trial was a double blind, dose-escalation, randomized, placebo-controlled, which was initiated after receiving all necessary regulatory and ethical clearances. The objectives of such a phase I trial are to evaluate the safety of the vaccine candidate and to gather preliminary results of immune responses induced by the candidate. The total duration of the trial was approximately 24 months. The volunteers recruited for this trial were 32 healthy, HIV-uninfected men and women between 18 and 50 years of age, from all socio-economic strata. Three intra-muscular injections of TBC-M4 or placebo were administered to the volunteers.

The results of the phase I vaccine trial of TBC-M4 suggest that further research is warranted. Currently two additional phase I trials testing the MVA-based candidate in a prime-boost regime are planned and under review by the relevant authorities in India and approved in the UK. The trials are designed to use different modes of administration of the priming vaccine, different dosages and different vaccine regimens. It is hoped that the prime-boost regimen will help to strengthen the modest immune responses observed in the phase I trial of the MVA-based candidate alone. Collectively the results will help determine whether and how to move forward with additional testing of this MVA-based AIDS vaccine candidate.