Pfs28 has been shown to induce antibodies that can block parasite development in mosquitoes. However, the protein is poorly immunogenic. Inspired by the success of the conjugation strategy for increasing the immunogenicity of Pfs25, we also developed a process to conjugate Pfs28 to rEPA. Various conjugation chemistries and methods were evaluated for optimal immunogenicity and most robust conjugation process. The biochemical properties of Pfs28-rEPA 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. In parallel, we are also conjugating Pvs28, an ookinete surface protein in Plasmodium vivax parasite and encoded by an ortholog gene of Pfs28, to rEPA. Pvs28-rEPA will be combined with Pfs25-rEPA as a two-component vaccine to broaden immune coverage and increase vaccine efficacy.
|Kubler-Kielb, Joanna; Majadly, Fathy; Biesova, Zuzana et al. (2010) A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates. Proc Natl Acad Sci U S A 107:1172-7|
|Qian, Feng; Aebig, Joan A; Reiter, Karine et al. (2009) Enhanced antibody responses to Plasmodium falciparum Pfs28 induced in mice by conjugation to ExoProtein A of Pseudomonas aeruginosa with an improved procedure. Microbes Infect 11:408-12|