This is an open label Phase 1 study of the Ad-PfCA vaccine designed to 1) provide reagents for the development and refinement of cell-mediated immunoassays for measuring the human immune response to candidate malaria vaccines (especially protective malaria vaccines such as DNA/Ad-PfCA where better assays are needed to identify the correlates of protective immunity) and 2) to provide a repository of antigen-specific PBMCs that can be used as positive and negative controls in cell mediated immunoassays. The study group will consist of up to 35 healthy adults aged 18 to 50 years who have been screened to meet inclusion and exclusion criteria.
Subjects will be eligible for participation regardless of baseline adenovirus 5 serostatus. At least 6 subjects will be "malaria naïve", meaning that 1) they have not been the recipient of a malaria vaccine, 2) they have no history of malaria infection or travel to a malaria endemic region within 6 months of first leukapheresis procedure or 60mL blood draw, 3) they have no history of long-term residence (\>5 years) in an area known to have significant transmission of P. falciparum, and 4) they have a negative P. falciparum circumsporozoite (PfCSP) ELISpot assay at baseline. (From herein, for simplicity, we refer to PfCSP simply as CSP). The remaining subjects will have no restrictions regarding receipt of malaria vaccines, travel history or baseline CSP ELISpot results. Although it is more difficult to recruit "malaria-naïve" subjects, the inclusion of at least 6 such subjects should provide a more varied array of immune responses; this may be helpful for assay development.
Eligible subjects will receive a single administration of the Ad-PfCA malaria candidate vaccine at a dose of 2 x 1010 pu by intramuscular injection. Approximately 1 month pre-immunization, study subjects will either have a large number of PBMCs collected by means of leukapheresis, or a simple 60 mL blood draw, dependent upon initial pre-screening. Pre-immunization samples designated for the repository do not require large volume sampling of PBMCs. Rather, a 60 mL whole blood draw is sufficient for repository purposes. Thus, subjects will be separated into sub-groups, dependent upon initial pre-screening. Subjects whose samples are designated for the repository will undergo a simple, 60 mL blood draw in lieu of leukapheresis #1 (sub-group A). Samples assigned for assay development will be obtained from sub-group B.
Approximately 1 month post-immunization, study subjects in both sub-groups will have PBMCs collected by means of leukapheresis. Consultation with immunology experts after post-immunization screening will assist to identify those subjects whose samples do not meet assay development or repository needs. In an effort to eliminate unnecessary procedures for subjects, these individuals will not undergo a second leukapheresis, but will return for their safety visit on day 84.
Prior to each leukapheresis/60 mL blood draw, a sample will be tested by CSP-ELISpot and AMA1 ELISpot; the results will be used to categorize samples (see below). Follow up visits will occur 2, 7, 14, 21, and 84 days following immunization. Depending on guidance from the FDA, subjects will then be followed annually by phone, email, or mailings up to five years from the time of immunization per FDA recommendation.
