UCT's candidate HIV vaccines ready for manufacture

DEVELOPMENT of three potential HIV vaccines developed at UCT will receive multi-million Rand support after showing promise in laboratory testing.

These vaccines will soon enter the manufacturing process and safety testing that precedes human clinical trials. The three candidate HIV vaccine products incorporate the genetic sequences of South African strains of HIV (subtype C), the most prevalent strain in the region. It is hoped that they will first prove safe and induce immune responses, and eventually show some protective properties in humans.

These candidate vaccines, developed by the Institute of Infectious Disease and Molecular Medicine (IIDMM) at UCT in conjunction with and funded by the South African AIDS Vaccine Initiative (SAAVI), now need to be produced in a manufacturing plant that can produce the products in a manner suitable for initial human clinical trials.

The National Institute of Allergy and Infectious Diseases (NIAID), the lead institute of the US National Institutes of Health (NIH) for HIV/AIDS research, has agreed to support the production of these vaccines at a cost that could reach approximately R20 million, while SAAVI will contribute R10 million to the manufacturing process. The vaccines will be manufactured in facilities in the UK and the USA.

The scientists at UCT, led by Professor Anna-Lise Williamson (who is jointly employed by UCT and the National Health Laboratory Services) and Professor Carolyn Williamson, have received funding from SAAVI since 2000 to produce a series of novel potential HIV vaccines. Funding has also been received from the government's Technology for Human Resources in Industry Programme (THRIP), the International AIDS Vaccine Initiative (IAVI) and the Poliomyelitis Research Foundation (PRF).

The vaccines that have been developed by the SAAVI/UCT group include two “DNA vaccines”, which express different HIV proteins; and, one 'MVA (Modified Vaccinia Ankara) vaccine' [MVA is a weakened (attenuated), safer form of the old smallpox vaccine which has been genetically engineered to produce HIV proteins in addition to its normal set of proteins]. It is planned that the vaccines will be tested individually and in combination, with the DNA vaccine used to “prime” or stimulate initial immune responses, followed by a MVA vaccine, which aims to 'boost' this anti-HIV immune response.

The scaled-up manufacturing process is extremely expensive, time consuming and technical. It involves bulk manufacturing; toxicity analyses to ensure product safety before human testing; and, a rigorous documentation process for submission to regulatory authorities like the Medicines Control Council (MCC) of South Africa and the US Food and Drug Administration (FDA).

“We need to proceed as rapidly as possible to phase I human clinical trials to test whether these candidate and other promising candidate vaccines are safe and of potential clinical benefit in preventing HIV infection or disease,” said Dr Tim Tucker, Director of SAAVI.

“The development of candidate HIV vaccines is a highly sophisticated, long-term task requiring international scientific collaboration and significant funding,” he continued. “This willingness of the NIAID to help provide support has facilitated a significant improvement in the time-lines for the manufacture and testing of these candidate vaccines.”

---

---