Works with the University of Lausanne in Switzerland on EVI P27A project
Northern Ireland-based contract development and manufacturing organisation Almac Group has taken a key role in preparing and delivering one of the longest synthetically produced protein fragments to be used as a vaccine in a Phase I clinical trial for malaria.
The European Vaccine Initiative (EVI), which is leading European efforts to develop effective, accessible and affordable vaccines against diseases of poverty, chose Almac to work on the P27A project based on the company's peptide synthesis expertise and capabilities, which enabled it to complete a significant milestone in the development of this vaccine.
The EVI’s primary objective was to assess the clinical safety and immunogenicity of the P27A protein as a malaria blood stage vaccine candidate. P27A is a 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 HPLC, which was challenging as this method did not scale-up effectively.
To address this issue, Almac linked up with the University of Lausanne, and developed an innovative size exclusion method as a preliminary purification prior to HPLC purification and counterion exchange to acetate. This process was applied to 50g of crude P27A to furnish the final peptide at approximately 90% purity. A total of 2,000 vials each containing 60µg were successfully produced and released for use in clinical trial.
In January last year, the two-centre 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, the trial proceeded to the target population in Tanzania at the Ifakara Health Institute. The initial results of the clinical study are expected early this year.
Stephen Barr, Managing Director of Almac's Sciences business unit, said: 'We are delighted with our innovative work on this project to enable us to deliver the long chain peptide vaccine for our client. Our collaborative approach taken with the University of Lausanne proved invaluable to combine our skills and talent to develop this unique solution.'