The purpose of this study is to assess the safety, tolerability, and immunogenicity of immunization with 2 doses of the PfCSP DNA vaccine (given 1 month apart) followed by a single dose of MVA.CSO (given either 1 month or 6 months later) when administered to healthy, malaria semi-immune adult volunteers. This Phase 1, randomized study conducted at Tetteh Quarshie Memorial Hospital will enroll 48 healthy volunteers, ages 18 to 50 years. Twenty four volunteers will initially be recruited and randomized to Groups 1 and 2. During Months 4 and 5 of the study, another 24 volunteers will be recruited and randomized to Groups 3 and 4. Group 1 will receive the DNA malaria vaccine intramuscularly (IM) at months 0 and 1, and the MVA malaria vaccine intradermally (ID) at month 7. Group 2 will receive a rabies vaccine IM at months 0 and 1, and a normal saline injection ID at month 7. Group 3 will receive the DNA malaria vaccine IM at months 5 and 6, and the MVA malaria vaccine ID at month 7. Group 4 will receive the rabies vaccine IM at months 5 and 6, and a normal saline injection ID at month 7. Blood samples will be collected at intervals for safety and immunogenicity studies. Vaccine safety will be monitored until 10 months after the final dose. At the conclusion of the study, volunteers randomized to Groups 1 and 3 will have the option of receiving the rabies vaccine. The primary study objectives are to: (1) assess the safety and tolerability of immunization with two doses of PfCSP DNA followed by one dose of MVA.CSO in healthy, malaria semi-immune adult volunteers when given at intervals of 0, 1, and 2 months or at 0, 1, and 7 months; (2) evaluate whether the PfCSP DNA/MVA.CSO prime/boost vaccine regimen induces PfCSP-specific immune responses, as assessed by IFN-gamma ELISPOT assay, over background responses; and (3) evaluate whether extending the interval between the second dose of PfCSP DNA and MVA.CSO from 1 month to 6 months is associated with higher levels of PfCSP specific T cell responses in semi-immune adults. The secondary study objective is to evaluate whether extending the interval between the second dose of PfCSP DNA and MVA.CSO from 1 month to 6 months is associated with higher levels of humoral immunity by ELISA and IFAT in semi-immune adults. The principal outcome measure will be the incidence of any vaccine related adverse event, abnormal lab values, and local or systemic reactions. An additional outcome variable for the remaining primary objectives is the results of the IFN-gamma ELISPOT assay at 1 week after administration of MVA.CSO. This study is planned to be the first of multiple clinical trials designed to test malaria vaccines in adults, children, and infants in endemic regions of Ghana.
Purpose
