It must have been a case of coincidence. Many important events of the AIDS vaccine trials jointly undertaken by the Government of India and the International AIDS Vaccine Initiative (IAVI) seem to be happening at the beginning of a year. It was in February last year that the Phase I clinical trial of the country’s first AIDS vaccine candidate got initiated when the first volunteer was injected at the National AIDS Research Institute (NARI), Pune. End January this year saw the enrolment of the thirtieth and the last volunteer required for Phase I trial at NARI. As if that were not sufficient, the Chennai Phase I clinical trial of another AIDS vaccine candidate got initiated on February 3 this year.
Completion of follow-up
And January next year would see the successful completion of the one-year follow-up of the last volunteer enrolled at NARI. “Decoding the data and finding out the outcome of the trial would not take much time as the number of volunteers is just 30,” said Ramesh S. Paranjape, Officier-in-Charge at NARI. If everything goes as per plan, getting to know the result of the Phase I clinical trial being conducted in Pune should be possible next year. “The results from this Phase I trial will be analysed jointly only when one year follow-up of the last vaccinated volunteer is completed in early 2007 and once all data are collected from the three [Belgium, Germany and India] countries,” noted Jean-Louis Excler, Senior Medical Director, IAVI, New Delhi.Phase I clinical trials using AAV vector were started in Belgium and Germany in December 2003 much ahead of the Pune trial. A vector is a virus that is used as a vehicle to carry HIV genes of interest. The Phase I trial is meant for studying the safety of the vaccine in humans and its ability to stimulate immune responses against HIV/AIDS. Data is also collected on the ideal dosage of the vaccine.Though many came forward to become volunteers (for the Pune trail), only 80 reached the final stage of medical examination before being accepted as volunteers. Of the 80, only 30 were found eligible. “Very small number [of volunteers] dropped out after being screened. Most [did not make it] because of medical reasons,” Dr. Paranjape said. According to him, almost equal numbers of men and women were enrolled. It may be recalled that enrolling volunteers is a time consuming and ongoing process and it took nearly a year for enrolling the requisite number. “We had no problem during the enrolling process,” Dr. Paranjape said.
This optimism is welcome as the Phase I clinical trial of yet another AIDS vaccine candidate using Modified Vaccine Ankara (MVA) vector has just been initiated at the Tuberculosis Research Centre (TRC), Chennai. In the case of Chennai, 32 volunteers would be enrolled and the process is expected to be completed in a year’s time. While the 30 volunteers in Pune were split into three groups to receive three different dosages (low, mid and high) of the vaccine candidate, volunteers in Chennai will have only two dosage groups (low and high). “For each dosage group [at NARI], each individual received only one injection. For TBC-M4 (MVA) at TRC, two dosage groups are planned, each participant receiving three injections,” Dr. Excler explained. “AAV and MVA are two different vectors with different intrinsic properties and whose dosage and dose to be used in humans are guided by data from animals studies and previous experience.” Dosage is the quantity of vaccine injected while dose is the number of injections.
The AIDS vaccine trials in India are based on placebo controlled study – some volunteers would get the vaccine while some others would be getting a placebo (a dummy). The volunteer and the person administering the injection will not know if the injection is a vaccine or a placebo. This is called a double blind study. And the process of selecting volunteers who will get a vaccine or placebo is randomised. In the case of the Pune trial, the 30 volunteers were split into three groups of 10 each. Of the 10, eight received the vaccine while two got a placebo. In the case of Chennai, the 32 volunteers will be split into two dosage groups (low and high) of 16 each. Of the 16, 12 volunteers will get the vaccine while the rest will get a placebo. The Adeno Associated Virus (AAV) vector used in Pune trial naturally infects about 60 per cent of humans in Europe and Northern America. It is however not known what percentage of the Indian population has naturally been infected by AAV and has developed antibodies against the virus. It is different in the case of Chennai trial. “MVA does not naturally infect humans. MVA is a vector derived from the vaccinia virus. People who have been immunised against smallpox with vaccinia may have developed an immune response that cross-reacts with the MVA vector,” Dr. Excler noted. “This possibility will be examined in this trial.”
Issue of protection
AIDS vaccine works on two strategies – either produce neutralising antibodies or cell mediated immune response. In the first case, the vaccine would be able to prime the immune system to kill HIV even as it enters the body. This in effect will prevent people from getting infected even when exposed to HIV. In the case of cell-mediated immune response, it is more a case of keeping the viral load under check and hence delay the progression to AIDS state. The MVA vector, like the AAV vector tried out in Pune, is designed essentially to elicit cell-mediated immune response in people not infected with HIV. “It [MVA vaccine candidate] may prevent people from becoming infected with HIV or may prevent people who later become infected from progressing to AIDS,” Dr. Excler elucidated. Results from the trials are expected to indicate the vaccine’s mode of action.