Malaria is a major parasitic disease in humans. Induction of immunity to the sexual stages, found in the mosquito host, is an important element in controlling the parasite. We have devised a conjugate vaccine by coupling protein or hapten-protein to very high molecular weight dextran. This highly multivalent construct induces rapid, persistent, high titer antibodies, in the absence of adjuvant, even in neonatal and immune- compromised animals. We propose to use this vaccine construct to induce transmission blocking antibodies to a key B cell epitope of the sexual stage specific protein pfs25. While pfs25 can induce blocking antibodies multiple immunizations with adjuvant are required. Furthermore, it has considerable homology to human epidermal growth factor. In phase I, we will evaluate the peptide conjugate vaccine for (1) optimal peptide orientation and valency, (2) suitable carrier proteins, (3) route of immunization and (4) ability of antibodies to bind recombinant protein. This technology can be applied to other peptide-based conjugate vaccines and may be particularly valuable in conjunction with sporozoite and merozoite peptide vaccines now in development.
| Lees, A; Nelson, B L; Mond, J J (1996) Activation of soluble polysaccharides with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate for use in protein-polysaccharide conjugate vaccines and immunological reagents. Vaccine 14:190-8 |
