Sporozoite Challenge of Polyprotein Vaccinees

Malaria infection kills over 2 million people each year. It is a major problem for those who live in endemic areas and for travellers. There is clearly a great need for a safe effective malaria vaccine.

The purpose of this study is to test the clinical efficacy of two candidate malaria vaccines (FP9-PP and MVA-PP). These live viral vector vaccines were administered in a 'prime boost' regime in the preceding trial VAC027.1.

Volunteers will now be exposed to 5 infective bites from mosquitoes carrying P. falciparum malaria.

This trial will:

• Measure efficacy as the time in hours from malaria exposure to blood film positive for malaria parasites
• Examine immunogenicity before and after malaria infection
• Measure longer term vaccine efficacy by re-challenging any protected volunteers 6 - 12 months later

Inclusion criteria

• Healthy non-pregnant adults aged 18 to 50 years
• The vaccinated group will be subjects who have received the vaccine regime described for group 6 or 7 in VAC027.1
• Resident in or near Oxford, UK for the duration of the challenge study
• For females only, willingness to practice effective contraception during the challenge study.
• Agreement to refrain from blood donation during the course of the study
• Written informed consent
• Willingness to allow the investigators to access hospital and General Practitioner medical notes
• Willingness to undergo an HIV test

Exclusion criteria

• Any deviation from the protocol-defined normal range in biochemistry or haematology blood tests or in urine analysis
• Prior receipt of an investigational malaria vaccine (unless administered in VAC027.1)
• Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
• Administration of chronic immunosuppressive drugs or other immune modifying drugs within six months of vaccination
• History of malaria chemoprophylaxis with chloroquine within 5 months prior to the planned challenge, with Lariam within 6 weeks prior to the challenge, and Riamet within 2 weeks prior to the challenge
• Any history of malaria
• Travel to a malaria endemic country within the previous 3 months prior to the planned challenge
• Planned travel to malarious areas during the study period
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia
• Evidence of cardiovascular disease
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of haemoglobinopathies
• History of diabetes mellitus
• Chronic or active neurological disease requiring ongoing specialist supervision
• Chronic gastrointestinal disease requiring ongoing specialist supervision
• History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
• Seropositive for hepatitis B surface antigen (HBsAg)
• Seropositive for hepatitis C virus (antibodies to HCV)
• Hepatomegaly, right upper quadrant abdominal pain or tenderness
• Evidence of serious psychiatric condition
• Any other on-going chronic illness requiring hospital specialist supervision
• Acute disease at the time of enrolment
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Pregnant or lactating female
• Female who is willing or intends to become pregnant during the study
• History of severe reactions or allergy to mosquito bites
• PI assessment of lack of willingness to participate and comply with all requirements of the protocol
• History or clinical evidence of intravenous drug abuse
• Any other finding which in the opinion of the investigator would significantly increase the risk of having an adverse outcome from participating in this protocol