Almac Group, the contract development and manufacturing organization, has reported on its role in preparing and delivering a synthetically produced protein fragment to be used as a vaccine in a Phase I clinical trial for malaria, which is being developed by the European Vaccine Initiative (EVI). EVI is leading European efforts to develop effective, accessible, and affordable vaccines against diseases of poverty, and the “P27A” project is focused on evaluating the clinical safety and immunogenicity of the P27A protein as a malaria blood-stage vaccine candidate.

P27A is an intrinsically unstructured, 104-amino acid long hydrophilic fragment derived from the Plasmodium falciparum malaria protein, PFF0165c. It presents only one mutation in more than 90 plasmodium strains. Specific human affinity purified antibodies are inhibitory in vitro parasite growth and the antibody response in donors living in endemic areas is associated with protection against malaria.

P27A was manufactured by linear solid phase peptide synthesis, using orthogonal Fmoc/tBu protecting group strategy. Development of the purification method of the crude protein fragment indicated that product of desired quality could be obtained by reverse-phase high-performance liquid chromatography (HPLC), which presented a challenge as this method did not scale-up effectively.

To address this issue, Almac combined its expertise and capabilities with the University of Lausanne, and developed a size-exclusion method as a preliminary purification prior to HPLC purification and counterion exchange to acetate. This process was applied to 50 g of crude P27A to furnish of the final peptide at approximately 90% purity. A total of 2,000 vials each containing 60 µg were successfully produced and released for use in clinical trial.

In January 2014, the two-center Phase I clinical trial of the P27A vaccine candidate started in Switzerland at the Centre Hospitalier Universitaire Vaudois, targeting adults from non-endemic areas. In August 2014, the trial proceeded to the target population in Tanzania at the Ifakara Health Institute. The initial results of the clinical study are expected in early 2015.

Source: Almac