Journal of Clinical Immunology, Vol. 16, No. 4, 1996 Special Article Malaria Vaccines ROBERTO AMADOR 1 and MANUEL E. PATARROYO 1 Accepted: January 2, 1996 Significant progress has been made in the development of the malaria vaccine during the last 20 years. Ninety percent of the 300-500 million clinical cases of malaria per year worldwide occur in Africa. Thus, research must be directed toward the 1 million African children under 5 years of age who die every year of malaria. An asexual blood-stage vaccine, capable of reducing severe and complicated malaria and malaria-related mortality, is therefore an important public health tool in these countries. Although knowledge of the parasite's biology is incomplete, research has allowed insight into some of the mechanisms that the parasite uses to evade host immunity. This is the basis for adopting an "antigenic cocktail" approach toward obtaining a synthetic or recombinant subunit vaccine such as the synthetic Colombian Malaria vaccine SPf 66. During the development of Spf66, field trials under both low and high malaria endemicity areas in Latin America and Africa have been carried out. The results from these studies showed a protective efficacy ranging between 38.8 and 60.2% against Plasmodium falciparum malaria. Given the characteristics of the normal immune response to malaria (relatively short-lived and not completely effective), it is understandable that the main goal is to try to increase the host's natural immunity. The best candidates for designing a malaria vaccine are the proteins required for parasite survival, those with low mutation rates and conserved epitopes. Because these proteins play an important role in multiple or alternative steps during the invasion process, they should be the targets against which a protective immune response should be elicited. The interaction between the ma- laria parasite and its host is complex. It is therefore crucial to define new ways of improving the immune response--such as directly modifying the chemical structure of epitopes or using new adjuvants or DNA immunization techniques--to produce novel vaccines against this disease. KEY WORDS: Malaria vaccine; immune response; molecular design. lInstituto de Inmunologfa--Hospital San Juan de Dios, Universidad Nacional de Colombia, Carrera 10 Calle 1, Santaf6 de Bogota, Colombia, SA. INTRODUCTION Significant contributions have been made in the devel- opment of the malaria vaccine during the last 20 years. The demonstration that irradiated sporozoites could offer complete protection to infection was proof that a vaccine was leasable. However, in vitro cultivation in large volumes proved a limiting factor in the production of a whole-parasite vaccine. A strategy based on the identi- fication and purification of different candidate molecules for malaria vaccines was therefore begun. The produc- tion of parasite material, and its purification and bio- chemical characterization, as well as studies of immune machanism of evasion of the parasite, were undertaken by research laboratories around the world. Knowledge of the parasite's biology is incomplete, but research has allowed insight into some of the mecha- nisms that the parasite uses to evade host immunity. From this still unclear picture, certain principles have been clarified for the development of a malarial vaccine. One of these is the necessity to adopt an "antigenic cocktail" approach to obtain a synthetic or recombinant subunit vaccine. Simple epitope or monovalent vaccines do not take into account the complexity of the parasite's life cycle. The synthetic Colombian malaria vaccine, Spf 66 (1-3), is an example of this cocktail methodology and the one that probably endorses the success of this approach. It is the first generation of multiantigenic, multistage synthetic vaccines and the first malaria vaccine to be safely innoculated into large groups of people. 183 STAGE-SPECIFIC MALARIA VACCINES The first approach in the development of a pre- erythrocytic vaccine was begun with the identification of 0271-9142/96/0700-0183509.5010 1996 Plenum Publishing Corporation