June 6-11, 2010
The development of a Plasmodium falciparum malaria vaccine is critical for future control and elimination programs. Recombinant protein based chemical conjugate vaccines, covering different parasite stages, are being developed due to complexity of the parasite and sub-optimal immunogenicity of recombinant malaria proteins in humans, respectively. Chemical conjugation of recombinant malaria proteins to carrier proteins improves their immunogenicity in animal studies. A transmission blocking vaccine comprised of the ookinete protein Pfs25 chemically conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) is currently being developed for pilot scale cGMP production. Bulk lots of Pfs25 and EPA have already been produced and released following cGMP. Appropriate analytical assays are being evaluated for both in-process and bulk release of the Pfs25-EPA conjugate vaccine. One critical assay already evaluated for determining the average mass is analytical size exclusion HPLC coupled with multi-angle light scattering. Phase 1 human clinical trials are planned for 2011. Another biological target of interest is the circumsporozoite protein (CSP), the most abundant and immunogenic protein on the surface of the sporozoite. A recombinant nearly full-length CSP has been produced in the methylotrophic yeast Pichia pastoris containing a bioengineered free thiol for chemical conjugation to various carrier proteins, including a chemically conjugated form of Pfs25. This recombinant protein based chemical conjugation platform, in combination with better adjuvant selection, will improve the potential for developing an efficacious malaria vaccine.
David L. Narum, Nicholas MacDonald, David Jones, Ruth Ellis, Yimin Wu, and Patrick E. Duffy, "DEVELOPMENT OF RECOMBINANT PROTEIN BASED CHEMICAL CONJUGATE MALARIA VACCINES TARGETING THE PRE-ERYTHROCYTIC STAGE, TRANSMISSION BLOCKING, OR BOTH" in "Vaccine Technology III", John G. Auniņš,Merck, USA; Barry C. Buckland, BiologicB, USA; Kathrin U. Jansen, Pfizer, USA; Paula Marques Alves, IBET, Portugal Eds, ECI Symposium Series, (2010). http://dc.engconfintl.org/vaccine_iii/5