Almac Group, the contract development and manufacturing organization, today announced its key role in preparing and delivering one of the longest synthetically produced protein fragment to be used as a vaccine in a phase I clinical trial for malaria.
European Vaccine Initiative (EVI) – who is leading European efforts to develop effective, accessible and affordable vaccines against diseases of poverty, chose Almac to work on the unique “P27A” project based on their extensive peptide synthesis expertise and capabilities enabling them to complete a significant milestone in the development of this vaccine.
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 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 HPLC which presented a challenge as this method did not scale-up effectively.
To address this issue, Almac combined their expertise and capabilities 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 of 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 2014, 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 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.
Stephen Barr, MD Almac’s Sciences business unit commented “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.”
Odile Leroy, Executive Director at European Vaccine Initiative “Collaborating with Almac has been an interesting and pleasant learning process on both sides, facing the technology challenges in a positive minded approach which was facilitated by an efficient project management”.
Find out more about Almac’s Peptide and protein service offering by visiting http://www.almacgroup.com/api-services-chemical-development/peptides-proteins/