Production, quality control, stability, and potency of cGMP-produced Plasmodium falciparum RH5.1 protein vaccine expressed in Drosophila S2 cells

Jin, Jing, Tarrant, Richard D., Bolam, Emma J., Angell-Manning, Philip, Soegaard, Max, Pattinson, David J., Dulal, Pawan, Silk, Sarah E., Marshall, Jennifer M., Dabbs, Rebecca A., Nugent, Fay L., Barrett, Jordan R., Hjerrild, Kathryn A., Poulsen, Lars, Jørgensen, Thomas, Brenner, Tanja, Baleanu, Ioana N., Parracho, Helena M., Thairi-Alaoui, Abdessamad, Whale, Gary, Moyle, Sarah, Payne, Ruth O., Minassian, Angela M., Higgins, Matthew K., Detmers, Frank J., Lawrie, Alison M., Douglas, Alexander D., Smith, Robert, de Jongh, Willem A., Berrie, Eleanor, Ashfield, Rebecca, and Draper, Simon J. (2018) Production, quality control, stability, and potency of cGMP-produced Plasmodium falciparum RH5.1 protein vaccine expressed in Drosophila S2 cells. NPJ Vaccines, 3. 32. pp. 1-29.

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Abstract

Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is a leading asexual blood-stage vaccine candidate for malaria. In preparation for clinical trials, a full-length PfRH5 protein vaccine called "RH5.1" was produced as a soluble product under cGMP using the ExpreS2 platform (based on a Drosophila melanogaster S2 stable cell line system). Following development of a high-producing monoclonal S2 cell line, a master cell bank was produced prior to the cGMP campaign. Culture supernatants were processed using C-tag affinity chromatography followed by size exclusion chromatography and virus-reduction filtration. The overall process yielded >400 mg highly pure RH5.1 protein. QC testing showed the MCB and the RH5.1 product met all specified acceptance criteria including those for sterility, purity, and identity. The RH5.1 vaccine product was stored at -80 °C and is stable for over 18 months. Characterization of the protein following formulation in the adjuvant system AS01B showed that RH5.1 is stable in the timeframe needed for clinical vaccine administration, and that there was no discernible impact on the liposomal formulation of AS01B following addition of RH5.1. Subsequent immunization of mice confirmed the RH5.1/AS01B vaccine was immunogenic and could induce functional growth inhibitory antibodies against blood-stage P. falciparum in vitro. The RH5.1/AS01B was judged suitable for use in humans and has since progressed to phase I/IIa clinical trial. Our data support the future use of the Drosophila S2 cell and C-tag platform technologies to enable cGMP-compliant biomanufacture of other novel and "difficult-to-express" recombinant protein-based vaccines.

Item ID: 57348
Item Type: Article (Research - C1)
ISSN: 2059-0105
Copyright Information: © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Funders: UK Medical Research Council (MRC), National Institute for Health Research (NIHR)
Projects and Grants: MRC grant MR/K025551/1
Date Deposited: 10 Mar 2019 22:45
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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