EP1300 Polyepitope DNA Vaccine Against Plasmodium Falciparum Malaria

Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium
(P.). It is estimated that there are 350-500 million clinical cases of malaria per year,
accounting for over one million deaths. The majority of deaths occur among children under
five years of age in Africa, especially in those areas with poor access to healthcare
services. Severe disease occurs most frequently with P. falciparum, at least partially due
to its ability to infect a higher percentage of erythrocytes and to adhere to capillary
walls. Development of a safe and effective vaccine targeting P. falciparum is a major public
health goal. To be truly effective in the general population, a vaccine should induce
responses targeting "immunologically" conserved regions. Epitope-based vaccines represent a
very logical approach to this problem because they can be designed to focus immune responses
only on conserved epitopes. The proposed clinical trial will be the first to evaluate a
novel deoxyribonucleic acid (DNA)-based, polyepitope vaccine against P. falciparum malaria.
The study will be conducted as a phase I, randomized, prospective, controlled,
single-center, dose-escalating trial. This study is designed to provide information
regarding the safety and tolerability of the EP (Electroporation) 1300 vaccine that will
allow further development of the vaccine in future studies. Immunogenicity will be assessed
in a preliminary fashion as a secondary endpoint. The primary objective of this study is to
evaluate the safety, reactogenicity and tolerability of the EP1300 (DNA) vaccine
administered via electroporation in healthy adult volunteers. The secondary objectives are
to obtain preliminary immunogenicity data for the EP1300 polyepitope DNA vaccine as assessed
by interferon-gamma enzyme-linked immunospot assay and to assess the tolerability of the
administration procedure in healthy volunteers. Thirty-nine healthy adults aged 18 through
40 who have no previous history of malaria exposure or infection, no history of travel to
malaria-endemic areas, and who have not received vaccines for malaria infection will be
enrolled in this study. Subjects will be randomized to receive 3 doses of either the DNA
vaccine or normal saline placebo at day 0, 28, and 56. DNA doses will be administered in
dose-escalating fashion from 0.25 mg to 4 mg. Dose escalation will proceed following a
review of all safety data up to and including the 2-week safety data time point following
the second immunization in the prior dosage group; review includes participation by Division
of Microbiology and Infectious Diseases and the Safety Monitoring Committee.