Use of a synthetic adjuvant in an effective vaccination of monkeys against malaria

Research towards the development of a vaccine against malaria has recently accelerated1, mainly because of a resurgence in the worldwide incidence of the disease2. These investigations have been aided by the use of the owl monkey for direct experimentation with human malaria3–5, techniques for producing Plasmodium falciparum antigen through continuous or shortterm in-vitro cultivation6,7, and the recent demonstration of effective immunization of owl monkeys against P. falciparum 8,9. However, the inclusion of a strong adjuvant in the vaccines seems to be required for the development of protective immunity. Thus, inclusion of the whole mycobacterial cell wall/mineral oil adjuvant (Freund's complete adjuvant: FCA)8,9 or a semi-synthetic derivative of the active component of that cell wall (6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-iso-glutamine: stearoyl-MDP)10,11 has been necessary for the successful immunization of primates against P. falciparum. The use of X-ray irradiated parasites12–14 or substitution of FCA by muramyl-dipeptide15,16 does not result in significant protective immunity. Because the systemic and local toxic responses to the active adjuvants is either unacceptable (as in the case of FCA)10,11, or essentially undescribed (as for stearoyl-MDP), it seemed highly desirable to attempt to identify alternative, well tolerated synthetic compounds with strong adjuvant activity for malarial vaccines. A potential candidate for this role was CP-20,961 (N,N-dioctadecyl-N′,N′-bis (2-hydroxyethyl)-propanediamine), a synthetic lipoidal amine, originally characterized as an interferon inducer17–20, with strong adjuvant activity for humoral and cellular immune responses21,22. We now report that killed P. falciparum merozoite antigen administered with CP-20,961 can effectively immunize owl monkeys against a lethal P. falciparum infection.