Questions and answers about the MVA.HIVA AIDS vaccine candidate in human trial in South Africa

What is MVA.HIVA?
MVA.HIVA is a preventive AIDS vaccine candidate. It is currently being tested in a small human trial in South Africa as well as in small trials in Kenya, Switzerland, Uganda and the United Kingdom.

A preventive AIDS vaccine like MVA.HIVA is intended to be given to people who are not infected with HIV, to prevent them from becoming infected and developing AIDS. A preventive vaccine would be different from therapeutics such as antiretroviral medicines, which are given to people who are already infected to help them live longer.

Who is researching MVA.HIVA?
MVA.HIVA is being researched by an international scientific partnership sponsored by the nonprofit International AIDS Vaccine Initiative (IAVI). The partnership includes:

• In South Africa, the South African AIDS Vaccine Initiative (SAAVI), Chris Hani Baragwanath Hospital and the Medical Research Council;
• In Kenya, the University of Nairobi and the Kenya AIDS Vaccine Initiative;
• In Switzerland, the University of Lausanne;
• In Uganda, the Uganda Virus Research Institute;
• In the United Kingdom, the University of Oxford, the Medical Research Council (MRC), Simbec Research Ltd., Imperial College of Science Technology and Medicine and King’s College.

MVA.HIVA was designed by the Kenyan, University of Oxford and UK MRC teams. Doses of MVA.HIVA for trials were manufactured by Impfstoffwerk Dessau-Tornau (IDT) GmbH in Germany.

How is MVA.HIVA intended to work?
MVA.HIVA is intended to be given to people who are not infected with HIV/AIDS, to elicit immune responses that would prevent them from becoming infected with HIV and developing AIDS. This may mean that someone who receives MVA.HIVA would be protected against becoming infected with HIV. Or it may mean that someone who receives MVA.HIVA and later becomes infected would be protected against developing AIDS.

More specifically, MVA.HIVA is intended to induce cytotoxic T cells (CTL) and other cell-mediated immune responses that are believed to be protective against HIV/AIDS. Researchers have observed similar immune responses in some individuals who have been repeatedly exposed to HIV but remain uninfected.

How is MVA.HIVA constructed?
MVA.HIVA consists of a synthetic copy of a small selection of HIV’s genetic material inserted into modified vaccinia Ankara (MVA) virus. More specifically, MVA.HIVA consists of a synthetic copy of a major part of HIV’s gag gene and 25 CTL epitopes. The MVA virus acts as a vector, or transport, for the gag gene and CTL epitopes.

Can MVA.HIVA cause HIV or AIDS?
Because MVA.HIVA does not contain HIV, it is impossible for it to cause HIV infection or AIDS. The MVA virus used in the candidate is a variant of the basis of a smallpox vaccine that has been safely administered to more than 100,000 people.

Where are trials of MVA.HIVA ongoing?
IAVI seeks to conduct trials of preventive AIDS vaccine candidates worldwide, in collaboration with the best researchers and facilities. Currently, MVA.HIVA is being tested in small human trials in South Africa, Kenya, Switzerland, Uganda and the United Kingdom:

• In South Africa, a trial of MVA.HIVA began in November 2003. The trial seeks to enroll volunteers across two sites, one in Soweto and the other in Durban. The trial is expected to last roughly 18 months.
• In Kenya, multiple trials of MVA.HIVA have begun, the first in February 2002. Trials are conducted in Nairobi.
• In Switzerland, a trial of MVA.HIVA began in November 2003 in Lausanne.
• In Uganda, a trial of MVA.HIVA began in February 2003 in Entebbe.
• In the UK, multiple trials of MVA.HIVA have begun, the first in March 2001. Trials are conducted in Oxford and London.

What are trials of MVA.HIVA testing?
All of the trials of MVA.HIVA that are now being conducted are small trials testing safety and whether the candidate induces immune responses. These trials are also comparing different doses and ways of administering the vaccine. If MVA.HIVA performs well in these small trials, it can advance to more and larger trials.

In some countries, but not South Africa, MVA.HIVA is being tested in combination with a second AIDS vaccine candidate, HIVA.DNA.

Who has oversight of trials of MVA.HIVA?
In each country where trials of MVA.HIVA are ongoing, permission to conduct the trials was granted by the governmental authority that regulates medical research as well as by independent review boards at the trial sites. For example, in South Africa, approval was granted by the Medicines Control Council and independent review boards at the Soweto and Durban sites.

As the sponsor of trials of MVA.HIVA, IAVI insists upon adherence to the highest international standards for conducting medical research. Volunteers must give informed consent before participating, they must receive counseling throughout the trial and they are free to leave the trial at any time for any reason. The personal information regarding each volunteer is held in the strictest confidence.

What other vaccine candidates are being researched?
MVA.HIVA is one design for a preventive AIDS vaccine. Other vaccine candidates, employing different designs and being researched by different teams, are now in human trials. IAVI estimates that more than two dozen different designs for a preventive AIDS vaccine are currently in trials. More are in the stage of research prior to trials.

For example, in South Africa, a second vaccine candidate named AVX101 is being tested in a small human trial. This trial, separate from the trial of MVA.HIVA but underway at the same sites in Soweto and Durban, also began in November 2003. AVX101 is being researched by AlphaVax Inc. and the US National Institutes of Health. IAVI provided support for the early development of AVX101.