mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice

mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice

Plasmodium vivax poses significant challenges to malaria control due to its relapsing nature. This study explores the immunogenicity and efficacy of nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccines targeting the P. vivax circumsporozoite protein (PvCSP). Two mRNA constructs encoding PvCSP...

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Main Authors: Amporn Limsalakpetch, Utaiwan Kum-Arb, Kosol Yongvanitchit, Rawiwan Im-Erbsin, Ratawan Ubalee, Norman Waters, Brian A. Vesely, Hiromi Muramatsu, Drew Weissman, Ying K. Tam, Shigeto Yoshida, John Adams, Anjali Yadava, Norbert Pardi, Sathit Pichyangkul
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: Oligonucleotides: Therapies and Applications
mRNA vaccine
nucleoside-modification
lipid nanoparticle
P. vivax
circumsporozoite protein
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253125001994
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Summary:Plasmodium vivax poses significant challenges to malaria control due to its relapsing nature. This study explores the immunogenicity and efficacy of nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccines targeting the P. vivax circumsporozoite protein (PvCSP). Two mRNA constructs encoding PvCSP were designed and tested in mice. Despite lower protein expression, the vaccine encoding the wild-type signal peptide (SP) and glycosylphosphatidylinositol (GPI) anchor of PvCSP induced significantly higher antibody titers against the PvCSP and its repeat region compared with the mRNA construct with SP but without GPI. The immunogenicity of PvCSP mRNA-LNP vaccines was evaluated using various administration routes and immunization schedules. Both intradermal and intramuscular delivery generated dose-dependent antibody responses, but the former demonstrated superior responses at a lower dose. Conversely, intravenous administration resulted in very poor responses. Notably, administering a delayed third dose intramuscularly 5 months after the second dose resulted in significantly higher levels of anti-repeat region antibodies and enhanced T cell responses in both the spleen and liver. This delayed regimen provided strong protection against sporozoite challenge, with the magnitude and avidity of anti-repeat region antibodies linked to this protection. These findings highlight the potential of the nucleoside-modified mRNA-LNP vaccine platform in combating P. vivax pre-erythrocytic stage infection.
ISSN:2162-2531

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