Malaria is a common and serious disease in young children that results in many childhood deaths. Although malaria is becoming less frequent in some parts of Africa as bed nets and anti-malarial drugs become more available, vaccines are still needed to prevent malaria as it is still a major problem.

Everywhere in the world, when new drugs or vaccines are being developed for children, research is first done in a few healthy adults, then in bigger numbers of healthy adults before children can finally be included. This malaria vaccine study is the same. Some studies involving small groups of adults in the UK, Gambia and Kenya and in older children in the Gambia have already been done and showed that the vaccine helps people to develop protection against malaria and had no serious side effects. We are now trying to conduct research on the vaccine with larger numbers of healthy adults.

We do not know whether the new malaria vaccine will protect people against infection, so particpants should take the usual measures to prevent malaria infection from mosquito bites during, and following the trial. These measures include the use of bed nets and seeking treatment for any illness including malaria.

In research to find out how well a vaccine is working, researchers usually have to compare two groups of similar people where only one group has been given the vaccine being developed. Both groups of people are followed up over time to see which group develops best protection against malaria. This allows us to understand how well the new vaccine is working.

In this study, we shall divide the participants into two groups. The new malaria vaccine will be given to one group and another vaccine that we know does not protect against malaria will be given to the other group. The vaccine we will use in the comparison group is rabies, which is a very useful vaccine that is already in use worldwide to protect people against the illness called rabies. Rabies can be caught from being bitten by an infected animal. People will be divided into the groups using a system based on chance without any preference, such that everyone has the same chance of being in either group. We hope to include 120 healthy adult men in this study, with 60 in each group.

Participants will be given either the new malaria or the rabies vaccine, depending on which group they are allocated to. Both vaccines will be given in two doses; the first in week 1(day 0) and the second in week 9(day 56). They will be asked to remain at the clinic for half an hour after each vaccination to check for any side effects. A field worker will visit them at home on the first day after each vaccination to check on their progress. If necessary, they will continue to visit participants at home daily until any symptom(s) have resolved. At this visit, the field worker will also ask questions about their use of bed nets in the home and will also ask for permission to check their bed net.

Participants will be asked to take anti-malarial drugs starting from week 10(day 63), in order to clear any malaria parasites that may be in their blood. It is possible to have malaria without having any symptoms. The anti-malarial drugs will be administered in the clinic over 3 days. They will also be required to come to the clinic should they be unwell and in need of anti-malarials, at any other time during the study period.

Blood sampling will be done several times as part of the research in order to check on how well the vaccine is working and how their body is reacting to the vaccine. Some blood samples will be taken from the arm and some from a finger prick. During these scheduled clinic visits, the clinician will also check on their health in general. There will be a total of 24 scheduled clinic visits.

 

Malaria transmission is falling in some parts of Africa as bednets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity.

Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).

The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies. It is important to determine efficacy before having larger trials in children.

We propose a Phase 2b study of 120 healthy adult men in Kenya. We will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. We also intend to assess the correlates of efficacy and natural immunity.