At a vaccines satellite meeting organised by the International AIDS Vaccine Initiative in Barcelona before the International Conference on AIDS, there were strong calls for a rethink on whether clinical trials always need to match vaccines to the subtype of the viruses circulating where a trial is to be held. The meeting also heard detailed updates on the slow progress that is being made towards new vaccines and preparation for more extensive clinical trials in a number of countries. (All presentations made at the conference are to be made available on IAVI´s website, through
Dr Jose Esparza, who leads WHO´s HIV vaccine work, said that the idea of "national vaccines" needs to be challenged, as it was threatening to become an obstacle to the development and future widespread use of an effective vaccine.
In fact, we do not know whether the differences between HIV subtypes will have any relevance for the effectiveness of vaccines against HIV. The answer to this question may also be different for vaccines that work in different ways.
Preliminary clinical research by the pharmaceutical company Merck using DNA and adenovirus vaccines that include only a single HIV gene sequence (gag, from a subtype B virus) is already showing immune responses that can destroy cells infected with HIV of other subtypes. This may also turn out to be true of other vaccines that are designed to promote cellular immune responses rather than antibodies.
Even in the case of antibodies, observed Dr Peggy Johnston of the US National Institutes of Health, we really have no idea which (if any) of the different laboratory tests that are now being used will predict the effectiveness of a vaccine in human beings.
If current efforts by IAVI and others can succeed in generating broadly neutralising antibodies, possibly those that bind to parts of the virus that perform essential roles, then by definition subtypes won´t matter. But even with vaccines of the type now in clinical trials in North America, the Netherlands, Puerto Rico and Thailand, we won´t know the answer without doing research.
The company, VaxGen, which is sponsoring those trials, has so far developed vaccines against subtype B and the recombinant AE virus circulating in Thailand. It has received funding from the US NIH to develop a subtype C version. However, if its vaccines were to prove successful when the first trial results are announced next year, the question would remain of what to do in regions such as West Africa where the epidemic is mainly driven by recombinants of subtypes A and G.
According to Dr Esparza, the best chance of getting answers to such questions is likely to be in regions such as East Africa, where multiple subtypes are circulating (A, C, and D are all present to varying extents). Here it might be possible to match a vaccine to one of the subtypes and then look at whether it gives better or equal protection against all of them. However, a study to prove this would need to be much larger than those planned up to now.
One of the main pressures against testing vaccines that don´t match local subtypes has been political, arising from sensitivities about populations in Africa and Asia being used to test vaccines that are designed for other and wealthier populations. The South African decision that they will only test new vaccines based on subtype C viruses is based on this and has helped to secure firm political support for their programme. The question activists, scientists and governments are all going to need to face, at some time, is whether and when this idea has outlived its usefulness and must give way to a serious effort to find hard data, one way or the other, on the issue.