AIDS vaccine research riding high
The announcement in March that the first AIDS vaccine candidate designed primarily for use in East Africa is entering human trials in Kenya, is just the latest in a series of encouraging events that has marked AIDS vaccine research over the past year or so. Hopes are running high that the current flurry of activity will produce a truly effective vaccine. Some experts, though, still licking the wounds of past disappointments, urge caution.
The Kenya vaccine was developed by a team of researchers from the University of Oxford, in the UK, and the University of Nairobi, in Kenya. It is based on the clade A variety of HIV, which is responsible for about 60% of HIV infections in East Africa. The Kenya trial is in the first, or Phase 1, stage of human tests and aims to determine the vaccines safety. A preliminary human trial was begun last August in Oxford, where the vaccine has been administered to 18 volunteers with no adverse effects to date. Work on the vaccine has been coordinated and funded by the New York-based International AIDS Vaccine Initiative (IAVI).
The vaccine will be given in a two-shot, prime-boost regimen. The first, priming, shot consists of HIV genes (naked DNA) injected directly into the vaccine recipient. The second, booster, shot uses a viral vector to carry HIV genes into the recipient. This vector, called Modified Vaccinia Ankara, is a version of vaccinia, the virus used to make the smallpox vaccine, but modified to prevent it from replicating in human cells.
The prime-boost approach is all the rage among vaccine researchers at the moment, as it shows good results in monkeys. A US research team from the National Institute of Allergy and Infectious Diseases (NIAID) and Emory University, in Atlanta, Georgia, recently reported that 23 of 24 monkeys given a prime-boost vaccine and then challenged with very high doses of SIV the monkey version of human HIV remained alive and well, whereas unvaccinated controls quickly developed AIDS related infections. The vaccinated animals were still infected, but had 2000 times lower levels of virus than the controls.
Professor Andrew McMichael, head of the Medical Research Councils human immunology unit at Oxford, where the Kenya vaccine was designed, says: The prime-boost approach is currently being tested in animal studies on several candidate vaccines which induce cellular immune responses, with or without antibodies. If two or three of these vaccines go all the way to Phase 3, well learn whether or not the approach works. It may be only partial protection. It may only be short-lived. But I think as soon as we get our foot in the door, we can lever it open. At the moment weve got nothing.
Commenting on the hopes raised by the launch of the Kenya vaccine trial, Dr José Esparza, coordinator of the WHO/UNAIDS HIV Vaccine Initiative, warns against going overboard: Ive been working in this field for ten years, he commented to the Bulletin. So Im a bit more cautious, and we should try to avoid creating too high expectations. This is just the first step of what could be a long journey.
Dr Peggy Johnston, director of AIDS vaccine research at the NIAID and, with a US$ 214 million annual budget for AIDS vaccine research and development, by far the largest funder of AIDS vaccine research worldwide, adds: Weve made tremendous strides in identifying several different candidate vaccines that induce good cellular immune responses in animal models. What we dont know is first of all, if they work in humans; second, if protection lasts; and third, and most important, if vaccinated individuals can still transmit infection. We want a vaccine that not only saves individuals but stops the virus spreading. Johnston says shed like to see more work on broadly reactive antibody responses. They could prevent initial infection, but thats a nut that hasnt been cracked yet she says.
Meanwhile, AIDS vaccine research, after several years in the doldrums, is on a roll, with funding on an upward spiral and the whole field flush with enthusiasm. The European Union has launched a new AIDS vaccine initiative, Eurovac, and France and Japan have their own programmes, along with the NIAID, IAVI, the Centers for Disease Control and Prevention, and the Walter Reed Army Institute of Research in the US, plus several groups in developing countries, including Brazil, India and South Africa. Pharmaceutical companies, such as Merck, GlaxoSmithKline and Wyeth Lederle, have also returned to the scene. And an African AIDS Vaccine Programme, uniting African researchers, is soon to be launched by WHO and UNAIDS.
With AIDS vaccine research burgeoning, both the NIAID and WHO see a growing need for coordination, especially for trials in Africa and other developing regions. The NIAIDs Johnston is pressing for international coordination, especially on developing common trial sites, while encouraging healthy competition amongst agencies and vaccine concepts.
As for WHO, Esparza says, we are an honest broker, bringing industry, agencies and countries together to do the trials, and building capacity for this long-term effort. But we need a system to make decisions, because in the past we have had products and even sites for trials, but no decision to move. The international community should have more to say on moving ahead with trials. These trials, Esparza says, should cover many more types of vaccine than the few currently in the research pipeline. Unfortunately, though, many of the labs and agencies are after the same products. This happens in the scientific community. Consensus is reached very quickly because everybody is reading the same scientific articles and following the same paradigms.
Robert Walgate, London