The past decade in malaria synthetic peptide vaccine clinical trials.

Over the past decade (2000-2009), there have been nine clinical trials of synthetic malaria peptide vaccines designed to target the pre-erythrocytic and erythrocytic stages of the Plasmodium falciparum parasite. Recent advances in parasite immunology and cell biology have been utilized to improve peptide design and adjuvant formulations. The clinical trials demonstrated the potential of second generation peptide vaccines to elicit antibodies that can neutralize sporozoite infectivity and cooperate with monocytes in ADCI to inhibit blood stage parasites. In addition, peptide-induced malaria-specific human CD4(+) and CD8(+) T cells were shown in vitro to have similar fine specificity and function as parasite-induced T cells. The results of these clinical trials, while encouraging, have emphasized the critical roles of immunological assays, in particular functional assays, for the evaluation of potential vaccine candidates. Additional challenges include the need for potent adjuvants for the development of synthetic peptide vaccines that can effectively target multiple stages of the Plasmodium parasite.