Malaria Vaccine Trials and Immunity
Vaccine Studies

All our vaccines undergo very strict toxicology studies before they can be used in human clinical trials. To date, various combinations and doses of the DNA, MVA and FP9 vaccines have been used safely in a number of human trials involving small numbers of volunteers, both in Oxford, UK and in The Gambia, West Africa with very encouraging results.

A volunteer receiving a vaccination
Trials to Date
Trial number Vaccine Regime No. of Vaccines No. challenged
VAC 01 DNA IM vs DNA gene gun +/- MVA boost 12  
VAC 02 MVA 6  
VAC 03 DDDM, DMM, DDD, MMM 15 12
VAC 04 Challenge study for VAC 03   5
VAC 05 DDMM vs GGMM 9 9
VAC 06 DDMM vs MMM in The Gambia 18  
VAC 07 Challenge study for VAC 05   5
VAC 08 MVA boosting of challenge controls 4  
VAC 09 MVA - safety study of higher MVA dose (1.5 x 108 pfu) 6  
VAC 10 DDDMM - higher dose DNA (2mg) + higher dose MVA, longer interval 9 9
VAC 11 MVA in children 1 to 5 in The Gambia 20 (+19controls)  
VAC 12 FP9 safety study and FFM i.e. FP9 twice followed by high dose MVA boost 12 5
VAC 13 Challenge study for VAC 10 and VAC 12   10
VAC 14 FFM, DDM, DDDM (all at higher doses) in The Gambia 29  
VAC 15 FFM vs MMM (all at higher doses) 17 16
VAC 16 Challenge study for VAC 15   5
VAC 17 DDFM, DDMF, FM, MF 17 17
VAC 18 RTS,S and MVA-CSO study: RRMcs, McsRR 24 (16)
VAC 20 Double-Blind Randomised Efficacy Trial of DDM with Rabies Controls 372 (1:1) ?
Vac 21 DDM-ME TRAP v. DDM-CS 16  
Vac 21.2 Challenge study for Vac 21   22
Vac 22.1 ICC-1132 in Seppic ISA 720 11  
Vac 22.2 Challenge study for Vac 22   17
Vac 23 FFM-CS and FFM-CS/ME-TRAP 32 21
Vac 24 FP9 ME-TRAP and MVA ME-TRAP in children 1 to 6 in Kenya 22  
Vac 25 FP9 CSO and MVA CSO in Kenya 20  
Vac 26 FP9 CSO and MVA CSO in The Gambia 32  
Vac 28 FP9 CS and MVA CS 21  
Vac 29 PCR diagnosis to evaluate pre-erythrocytic malaria vaccines 102  

D DNA vaccine (intramuscular)
M MVA vaccine (intradermal)
F FP9 vaccine (intradermal)

Each vaccination regime involves at least two different types of vaccine and these are given at three to four week intervals. After each vaccination, we see our volunteers one week later to measure the immune response that they have made to the vaccine. The first type of vaccine given "primes" the immune system and the second type of vaccine "boosts" the immune response.

The Challenge Study

After vaccination, it is important to see whether the vaccines are able to protect people against malaria. In order to do this we infect our volunteers with a fully drug-sensitive strain of malaria using a very safe and well-established procedure at Imperial College in London. In addition to vaccinated volunteers, we also have a number of unvaccinated controls take part in the challenge study to make sure that the infection system works and to act as a comparison.

Volunteers are exposed to the bites of five malaria-infected mosquitoes. These mosquitoes are placed in paper cups onto which the volunteers rest their arm for five minutes.

A volunteer in the challenge study

mosquitoes carrying the malaria parasite

Clearly, untreated malaria could be very serious and so the volunteers are followed-up very carefully in our clinic (up to twice per day). At each of these visits a blood sample is taken and examined for malaria. At the first sign of malaria, the volunteer is immediately treated with the anti-malarial drug chloroquine. However, if the volunteer is completely protected by the vaccine they will not develop malaria.

A malaria blood film
Image from the Wellcome Trust courtedy of Bruce-Chwatt LJ
Microscopic appearance of malaria infection
Image from Liverpool School of Tropical Medicine

The aim of the malaria challenge study is to establish whether our vaccination regimes offer protection against malaria infection. Protection may be 'partial' or 'complete':

Complete protection is where our vaccinated volunteers do not develop malaria in the challenge study. Naturally, all the unvaccinated control volunteers have to develop malaria so that we are confident that the infection system has worked.

Partial protection is where there is a delay in the onset of malaria in the vaccinated volunteers compared to the unvaccinated controls. This means that the body's immune system is controlling the infection to start with but is ultimately overwhelmed. Partial protection seen in the UK may turn into a more significant degree of protection in Africans who have already been exposed to malaria.

Our Results
Using different combinations of our malaria vaccines we have been able to completely protect some volunteers against malaria infection. Other volunteers have been partially protected against malaria. This is clearly very exciting progress although there is more work to do and larger field studies to be planned.