Though Pfs25 has been shown to induce antibodies that can block parasite development in mosquitoes, the protein is poorly immunogenic. Thus the major challenge facing Pfs25-based TBV development is to increase the immunogenicity and response longevity. Immunologists have known for a long time that chemically cross-linking a poor protein immunogen to itself increases its immunogenicity. In collaboration with Drs. John Robbins and Rachel Schneerson at the Laboratory of Developmental and Molecular Immunology of the NICHD, we are developing a conjugate vaccine that consists of Pfs25-Pfs25 conjugates. Various conjugation chemistries and methods were evaluated for the highest immunogenicity and most robust conjugation process. The biochemical properties of Pfs25-Pfs25 were characterized and the conjugates were evaluated in animals for their immunogenicity. The immune sera induced by the conjugate vaccine were tested for their ability to block parasite development in mosquitoes. A Phase 1 trial has been planned to test the safety, immunogenicity, and ex-vivo transmission blocking activity in humans.
| Wu, Yimin; Ellis, Ruth D; Shaffer, Donna et al. (2008) Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS ONE 3:e2636 |
| Kubler-Kielb, Joanna; Majadly, Fathy; Wu, Yimin et al. (2007) Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. Proc Natl Acad Sci U S A 104:293-8 |
