Kevin Marsh, director of the Wellcome-KEMRI-Oxford Collaborative Research Programme, discusses malaria vaccines on this MVI guest blog:
Deciding when it’s a good time to take a malaria vaccine into African countries for testing in children is not always straightforward. It’s a real issue for vaccine developers and funders and one that is the subject of debate here at MIM and in the wider malaria vaccine community. There are no absolute criteria for these decisions.
For malaria vaccines, the ability to challenge—with the bites of infected mosquitoes—healthy adult volunteers who have not previously been exposed to malaria is a critical way for developers to decide whether or not a candidate vaccine has potential and should therefore move to African trials.
For pre-erythrocytic vaccine candidates—those designed to prevent the parasite from getting past the liver and into the blood stream—this model has proven to be extremely valuable. One good example is RTS,S, the vaccine candidate developed by GlaxoSmithKline Biologicals and supported by the PATH Malaria Vaccine Initiative that is now being tested in the region.
On the other hand, for vaccines that target the parasite later in its life cycle, during its development in human red blood cells, the human challenge model has been seen to have limitations. However, many researchers now believe these limitations can be overcome and that challenge models should form part of the selection pathway for blood-stage vaccines. Without this crucial decision point, a major question is, how do developers decide which blood-stage vaccines should go into the field?
An added complication for these blood-stage vaccine candidates is the fact that adults tend to develop immunity as a result of previous exposure to the parasite. Therefore, young children who have had limited exposure and limited immunity to malaria are really the best population for evaluating whether these vaccines work.
These factors create ethical dilemmas for developers and funders, given that vaccine candidates that have limited human proof-of-concept data may need to be evaluated in large numbers of children.
All the important challenge models exist in developed countries. So it’s time to ask why such models are not found in developing regions, such as Africa. In Kenya, there are active discussions among ethical and research institutions to examine whether this country could take a lead in developing challenge models. There’s a strong positive feeling that this is important.
In the meantime, there needs to be broad consensus among scientists, including African scientists, about when vaccines should be tested in Africa. It’s also important that African institutions and scientists are meaningfully involved throughout the process of vaccine development.