Preclinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice

Multiple antigen peptides (MAPs) containing epitopes of the major surface p rotein of the malaria sporozoite, the circumsporozoite (CS) protein, have b een shown in previous studies to elicit antibody-mediated protection agains t sporozoite challenge in experimental murine and simian hosts. For the pre paration for a phase I trial of a P. falciparum (T1B)(4) MAP, which contain s T and B cell epitopes from the CS repeat region, pre-clinical immunogenic ity and adjuvant formulation studies were carried out in mice and Aotus mon keys. The (T1B)4 MAP was found to be immunogenic in three different species of owl monkeys, Aotus nancymae, A. vociferans and A. nigriceps. Optimal an tibody responses were obtained in A. nancymae immunized s.c. with (T1B)(4) MAP emulsified in Freund's, in which peak titers of over 10(6) were obtaine d in individual monkeys. MAP immunized A. vociferans also developed high le vels of anti-sporozoite antibodies, although the kinetics and the magnitude of the response differed from A. nancymae. (T1B)(4) MAP adsorbed to alum ( aluminum hydroxide), a formulation that is acceptable for human use, was le ss immunogenic in naive A. nancymae, as well as A. nigriceps. The injection of MAPs/alum, however, significantly enhanced antibody responses in sporoz oite-primed monkeys, suggesting that the administration of the MAP vaccine may be an effective means to increase the low levels of antibody present in individuals living in malaria endemic areas. The addition of a co-adjuvant QS-21, a purified saponin, significantly increased the immunogenicity of t he alum-adsorbed MAP in both mice and monkeys, providing a vaccine formulat ion suitable for phase I trials in human volunteers. (C) 1999 Elsevier Scie nce Ltd. All rights reserved.