Development of Sporozoite Vaccines

Protective immunity against malaria has been achieved in hosts ranging from birds to man by repeated inoculation of irradiated sporozoites. The main antigens involved in protective immunity to sporozoites are the circumsporozoite (CS) proteins, which are part of a family of proteins, covering the whole surface membrane of the parasite, and which have similar physico-chemical and antigenic properties. Monovalent fragments of monoclonal antibodies to CS proteins neutralize sporozoite infectivity. All monoclonal antibodies recognize a single immunodominant region within the various CS proteins, and this region contains repetitive epitopes. The recurrent immunodominant epitope of the CS protein of P. knowlesi has been identified, and shown to consist of 12 tandemly repeated subunits of 12 amino acids. The dimer of the dodecapeptide was coupled to protein carriers, emulsified in Freund's complete adjuvant, and injected into rodents and monkeys. All animals made anti-peptide antibodies, and most of the antisera reacted with P. knowlesi CS protein.