Prime-boost vaccination involves giving one vaccine (prime), followed by or together with a second type of vaccine (boost). A prime-boost combination may induce different types of immune responses and/or enhance overall responses induced by either type of vaccine alone. In the proposed prime-boost trial, it is expected that this strategy would increase the magnitude (a little bit like the height of a protecting wall) of the response and its breadth (the thickness of the wall).


Previous Phase I studies, testing different vaccine candidates, indicate that a DNA vaccine in a prime-boost combination generates enhanced immune responses compared to a single vaccine regimen without the DNA vaccine. Previous Phase I studies with a prime-boost regimen of different DNAMVA combinations showed that it was well tolerated, and generated favourable immune responses. The TBC-M4 vaccine was tested recently in a Phase I trial and found to be well-tolerated and able to generate immune responses in most volunteers, in the case of the low-dose vaccine, or all volunteers, in the case of the high-dose vaccine. These results warranted further investigation. In studies of DNA + MVA vaccines in nonhuman primates using the SIV model, immunized non-human primates control-

-led SIV replication, providing an important preclinical test of concept for this vaccine strategy.


The trial is designed to recruit 32 healthy HIV-negative male or female volunteers 18 to 50 years of age, who report that they are at low risk for HIV infection.


The trial is conducted according to established international guidelines for ethical treatment of all volunteers in pharmaceutical and vaccine trials. All potential volunteers will be counseled on informed consent – a written agreement to participate in a trial based on the volunteer's complete understanding of all relevant information. Throughout the trial, volunteers will receive extensive counseling on how to reduce their risk of exposure to HIV, as well as access to prevention methods such as condoms. A volunteer can decide to leave the study at any time without explanation.

All the necessary clearances for the trial have been received from the NARI and TRC Ethics Committees, NARI and TRC Scientific Committees, Genetic Engineering Approval Committee, Drug Controller General of India (DCGI) and Health Ministry's Screening Committee. The trial will also be monitored by an independent Safety Review Board.

The trial is not designed to test the ability of the vaccine candidates to protect against HIV infection or to slow progression of disease. A Phase I trial is the first stage of human testing. In this case, the trial will assess the safety and tolerability and immune responses elicited by the ADVAX and TBC-M4 vaccine candidates in a prime-boost regimen. If the results are promising, further testing will be considered.