Accelerating the clinical development of protein-based vaccines for malaria by efficient purification using a four amino acid C-terminal ‘C-tag’

Autor: Jin, J, Hjerrild, KA, Silk, SE, Brown, RE, Labbé, GM, Marshall, JM, Wright, KE, Bezemer, S, Clemmensen, SB, Biswas, S, Li, Y, El-Turabi, A, Douglas, AD, Hermans, P, Detmers, FJ, de Jongh, WA, Higgins, MK, Ashfield, R, Draper, S
Rok vydání: 2017
Předmět:
Zdroj: International Journal for Parasitology.
ISSN: 0020-7519
DOI: 10.1016/j.ijpara.2016.12.001
Popis: Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example. To that end, we have previously reported the expression of a novel protein vaccine for malaria using the ExpreS(2)Drosophila melanogaster Schneider 2 stable cell line system, however, a very low overall process yield (typically 85% recovery and >70% purity in a single step purification directly from clarified, concentrated Schneider 2 cell supernatant under mild conditions. Biochemical and immunological analysis showed that the C-tagged and hexa-histidine-tagged P. falciparum reticulocyte-binding protein homolog 5 proteins are comparable. The C-tag technology has the potential to form the basis of a current good manufacturing practice-compliant platform, which could greatly improve the speed and ease with which novel protein-based products progress to clinical testing.
Databáze: OpenAIRE