Both the National AIDS Research Institute (NARI) in Pune and the Tuberculosis Research Centre (TRC) in Chennai have a wealth of experience in conducting clinical trials. Both have previously conducted Phase I AIDS vaccine clinical trials. Both clinical trial centres house state-of-theart laboratory facilities. AIDS vaccine candidates in development need to be tested in a variety of settings, which is why IAVI and others test vaccine candidates in multiple regions across the world, including those regions where an AIDS vaccine is most needed. TBC-M4 and ADVAX are also being tested in a prime-boost regimen in a separate Phase I trial in the UK.


It is not yet known if the ADVAX plus TBC-M4 combination will protect against HIV infection or slow progression of disease, and this trial is not designed to test efficacy.

This is a Phase I trial designed to test the safety and preliminary immune responses of the prime-boost vaccine regimen. The results will be evaluated at the conclusion of the trials to determine whether the candidate merits further testing. Ultimately, the disgoal is to find a vaccine
that would work anywhere in the world.

For both vaccine candidates, extensive safety data has been collected in animal studies. The vaccine candidates have also been tested individually in Phase I human studies and were found to be safe and well tolerated. Previous Phase I studies with different DNA-MVA AIDS vaccine combinations demonstrated that these prime-boost regimens were safe and well tolerated.


It is not known if this prime-boost combination can protect against HIV infection. The purpose of this Phase I trial, an initial human test conducted with a small group of people, is to gather safety data and preliminary results on the immune responses induced by the vaccine candidate. A Phase I trial does not test the efficacy of a vaccine. If initial results warrant (meaning the candidates produce different or better responses than candidate vaccines that have failed in efficacy tests), further safety and efficacy tests are conducted at a later stage in the product development process with a large group of volunteers to determine whether the vaccine candidate prevents HIV infection and/or disease.


Just as it is not yet known if this primeboost combination will be able to help protect against HIV infection or slow progression of disease, the same is true for other AIDS vaccine candidates currently in clinical trials. The different DNA and MVA-based AIDS vaccine candidates differ in their design and manufacturing and quality control process.

This result was disappointing but not surprising, given the nature of pharmaceutical product development, in which the vast majority of candidates never advance past Phase I and Phase II trials to efficacy testing. Of all the AIDS vaccine candidates that have been developed, only three have advanced to efficacy testing.



Studies of effects of vaccine candidates on disease have to use an animal model, the simian immunodeficiency virus (SIV), and SIV vaccines rather than HIV vaccines; these studies may not precisely predict the potential of vaccine candidates to provide benefits in humans. It is therefore difficult to say precisely how ADVAX and TBC-M4 compare to other DNA and MVA-based AIDS vaccine candidates and to alternative approaches. However, despite these limitations, the results obtained in the previous TBC-M4 Phase I trial are promising, and the prime-boost trial aims to gather additional understanding of the promise of this vaccine candidate alone and in combination with ADVAX. No DNA vaccine candidate has been tested in large-scale trials. There is an efficacy trial ongoing in Thailand to evaluate a prime-boost combination of two AIDS vaccine candidates called AIDSVAX and ALVAC. The Thai trial is proceeding well, no harm has been detected by the independent monitoring committee. It will end next year. Nothing is known yet about the efficacy of the candidates tested.