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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

19 Citationer (Scopus)
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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®, with or without Matrix-MTM, elicited functional antibodies that reduced transmission to mosquitoes and sporozoite invasion of human hepatocytes. Altogether, our data support manufacture and clinical evaluation of ProC6C as a multistage malaria-vaccine candidate.

OriginalsprogEngelsk
Artikelnummer120
Tidsskriftnpj Vaccines
Vol/bind6
Antal sider11
DOI
StatusUdgivet - 2021

Bibliografisk note

© 2021. The Author(s).

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