Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
12 Oct 2021
12 Oct 2021
Historique:
received:
04
03
2021
accepted:
17
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
14
10
2021
Statut:
epublish
Résumé
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
Identifiants
pubmed: 34642303
doi: 10.1038/s41541-021-00383-8
pii: 10.1038/s41541-021-00383-8
pmc: PMC8511065
doi:
Types de publication
Journal Article
Langues
eng
Pagination
120Subventions
Organisme : European and Developing Countries Clinical Trials Partnership (EDCTP)
ID : RIA2018SV-2311
Organisme : European and Developing Countries Clinical Trials Partnership (EDCTP)
ID : RIA2018SV-2311
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 733273
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 733273
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 733273
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 733273
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : NNF14CC0001
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : NNF14CC0001
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : NNF14CC0001
Organisme : PATH (Program for Appropriate Technology in Health)
ID : OPP1108403
Informations de copyright
© 2021. The Author(s).
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