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Singh SK, Plieskatt J, Chourasia BK, et al. Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ Vaccines. 2021;6(1):120doi: 10.1038/s41541-021-00383-8.
Singh, S. K., Plieskatt, J., Chourasia, B. K., Singh, V., Bengtsson, K. L., Reimer, J. M., van Daalen, R. C., Teelen, K., van de Vegte-Bolmer, M., van Gemert, G. J., Jore, M. M., & Theisen, M. (2021). Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ vaccines, 6(1), 120. https://doi.org/10.1038/s41541-021-00383-8
Singh, Susheel K, et al. "Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine." NPJ vaccines vol. 6,1 (2021): 120. doi: https://doi.org/10.1038/s41541-021-00383-8
Singh SK, Plieskatt J, Chourasia BK, Singh V, Bengtsson KL, Reimer JM, van Daalen RC, Teelen K, van de Vegte-Bolmer M, van Gemert GJ, Jore MM, Theisen M. Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ Vaccines. 2021 Oct 12;6(1):120. doi: 10.1038/s41541-021-00383-8. PMID: 34642303; PMCID: PMC8511065.
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NPJ Vaccines. 2021 Oct 12;6(1):120. doi: 10.1038/s41541-021-00383-8.

Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine.

NPJ vaccines

Susheel K Singh, Jordan Plieskatt, Bishwanath K Chourasia, Vandana Singh, Karin Lövgren Bengtsson, Jenny M Reimer, Renate C van Daalen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Matthijs M Jore, Michael Theisen

Affiliations

  1. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  2. Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
  3. PATH's Malaria Vaccine Initiative, Washington, WA, USA.
  4. Novavax AB, Uppsala, Sweden.
  5. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands.
  6. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands. [email protected].
  7. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. [email protected].
  8. Centre for Medical Parasitology at Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. [email protected].

PMID: 34642303 PMCID: PMC8511065 DOI: 10.1038/s41541-021-00383-8

Abstract

The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are leading candidates for a malaria transmission-blocking vaccine (TBV). Previously, we showed that a Pfs230-Pfs48/45 fusion protein elicits higher levels of functional antibodies than the individual antigens, but low yields hampered progression to clinical evaluation. Here we identified a modified construct (ProC6C) with a circumsporozoite protein (CSP) repeat-linker sequence that enhances expression. A scalable and reproducible process in the Lactococcus lactis expression system was developed and ProC6C was successfully transferred for manufacturing under current Good Manufacturing Practices (cGMP). In addition, a panel of analytical assays for release and stability were developed. Intact mass spectrometry analysis and multiangle light scattering showed that the protein contained correct disulfide bonds and was monomeric. Immunogenicity studies in mice showed that the ProC6C adsorbed to Alhydrogel

© 2021. The Author(s).

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