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

Abstract

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 malaria^3–5, techniques for producing Plasmodium falciparum antigen through continuous or shortterm in-vitro cultivation^6,7, 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 parasites^12–14 or substitution of FCA by muramyl-dipeptide^15,16 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 inducer^17–20, with strong adjuvant activity for humoral and cellular immune responses^21,22. 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.