Heightened South African activity in HIV vaccine research
Cape Town, 19 October 2015 – There are clinical trials in process in communities in South Africa and other southern African countries which aim to advance the insights gained from the only HIV vaccine study yet to show some efficacy in protecting humans from infection. That study, known as RV144, was conducted in Thailand by the US Military HIV Research Program with support from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health in the US. It enrolled more than 16 000 volunteers.
The southern African studies include the HVTN 100 study which is a critical step along the path to possible licensure of a vaccine regimen similar to the one used in the Thai trial. This trial, taking place exclusively in South Africa, will establish whether the regionally adapted and modified vaccine regimen can produce a more powerful and durable immune response against HIV.
The vaccine regimen tested in the Thai trial found that participants who received the vaccine were 31.2% less likely to be infected with HIV after a period of 3.5 years than participants who received a placebo. The RV144 vaccine regimen had an even higher efficacy (approximately 60%) one year after vaccination.
HVTN 100 started in February this year and by the end of May all participants (252) had been enrolled. While this study tests a candidate vaccine regimen with canary pox virus and protein components similar to that used in RV144, a different adjuvant is being introduced in the South African study, in order to enhance the effect of the vaccine in the body, and an extra vaccination will be given to boost and prolong the effect of the vaccine. The candidate vaccine components have also been modified to reflect the particular HIV sub-type (clade C) that predominates in southern Africa. Participants will remain in the study for a year and a half, and receive a total of eight injections of vaccine or placebo at five different time points during this period.
If HVTN 100 yields promising results, a further study involving more than 5 000 voluntary participants in South Africa would be launched in mid- to late-2016. The purpose of this large Phase IIb “pivotal” study would be to test whether the more powerful and prolonged immune response produced in HVTN 100 translates into higher levels of protection against HIV than the modest 31.2% seen in the Thai trial.
“Because vaccines can be applied across entire populations, a successful HIV vaccine would be the most powerful weapon imaginable against the HIV pandemic,” says Professor Glenda Gray, Co-Principal Investigator of the HIV Vaccine Trials Network (HVTN)*, which is conducting the southern African studies, and Director of its Africa Programme. “But the requirements for an effective vaccine are also particularly demanding: it must be extremely safe and provide a high level of protection, as well as being long-lasting and relatively easy to administer to large numbers of people.”
The safety of the Thai trial vaccines in the South African population was established in an earlier trial, HVTN 097, which released its findings a year ago.
Professor Linda-Gail Bekker, Principal Investigator of HVTN 100**, emphasises that every step along the path to possible licensure of the world’s first HIV vaccine will be stringently evaluated. “In the middle of next year we will be making some far-reaching decisions whether to proceed to the final stage of research on the study vaccine regimen. As scientists, our job will be to listen closely to what the results of HVTN 100 are telling us and to resist any temptation to be swayed by the desperate need for a vaccine to prevent HIV.”
Preparation is also well underway for other HVTN vaccine studies in southern Africa. These are early stage human trials that will not impact directly on the potential licensure of the modified RV144 vaccine regimen. However, these studies have utilised scientific clues provided by the Thai trial to select new candidate vaccines for testing to establish their safety and the strength of the immune responses they elicit. These trials will compare the performance of the various candidate vaccines when used in different regimens – with different boosters and adjuvants and even with different delivery methods.
The studies are part of a larger HVTN research track that aims to identify the most promising new vaccine regimens for potential further development and future use in large scale efficacy trials. Some of the studies will commence in late 2015 and others in 2016. They are:
HVTN 107, which will involve 132 participants in South Africa, Mozambique and Zimbabwe.
HVTN 108, which aims to enrol 334 participants and will take place in South Africa and the US.
HVTN 111, involving 132 participants, which will be undertaken in South Africa, Malawi, Zambia and Tanzania.
HVTN 113, the largest of the trials with 380 volunteers, which will include sites in South Africa, Malawi, Tanzania, Zambia and Zimbabwe.
These critical HIV vaccine trials are being conducted by the HVTN as a partner in the unique Pox Protein Public Private Partnership (P5), comprising a diverse set of public and private organisations, including NIAID, the Bill & Melinda Gates Foundation, the South African Medical Research Council, Novartis Vaccines and Diagnostics, and Sanofi Pasteur. The trials are co-funded by NIAID and the Bill & Melinda Gates Foundation. The P5 was established five years ago to build on the promise of the RV144 trial with a view to developing a vaccine that could have a significant impact on public health in southern Africa.
An important spin-off of the P5 programme is the development of the new Cape Town HIV Immunology Laboratory (CHIL). This opened in 2013 and provides significant support to its studies, offering training and employment opportunities for local scientists and high-level technicians.
*Professor Gray is also President of the MRC. **Professor Bekker is also deputy director of the Desmond Tutu HIV Centre.
The HIV Vaccine Trials Network (HVTN) is the largest worldwide clinical trials network dedicated to the development and testing of HIV/AIDS vaccines. The HVTN is an international collaboration that conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. Support for the HVTN comes from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH). The Network’s HIV Vaccine Trial Units are located at leading research institutions in 27 cities on four continents. The Network’s headquarters are at the Fred Hutchinson Cancer Research Center in Seattle, Washington.