rCSP in various lengths were expressed in P. pastoris and E. coli, and processes for scaled recovery were developed. Processes were developed to chemically conjugate the rCSPs to recombinant EPA and CRM197, the carrier proteins with demonstrated capacity of immune enhancement for polysaccharide antigens. B- and T-cell responses, induced by the conjugates in several formulations were evaluated in rodent models. Whereas conjugation significantly increase the antibody responses to the rCSP, a novel adjuvant containing TLR4 agonist significantly increase cellular response in rodents. Studies are also being conducted in non-human primates to evaluate immunogenicity of these vaccine candidates, which will be used as go/no go criteria before advancing to trials in humans.
|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|
|Plassmeyer, Matthew L; Reiter, Karine; Shimp Jr, Richard L et al. (2009) Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. J Biol Chem 284:26951-63|