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A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax.
Kunkeaw, Nawapol; Nguitragool, Wang; Takashima, Eizo; Kangwanrangsan, Niwat; Muramatsu, Hiromi; Tachibana, Mayumi; Ishino, Tomoko; Lin, Paulo J C; Tam, Ying K; Pichyangkul, Sathit; Tsuboi, Takafumi; Pardi, Norbert; Sattabongkot, Jetsumon.
Affiliation
  • Kunkeaw N; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Nguitragool W; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Takashima E; Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Kangwanrangsan N; Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
  • Muramatsu H; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • Tachibana M; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Ishino T; Division of Molecular Parasitology, Proteo-Science Center, Ehime University, Toon, Japan.
  • Lin PJC; Department of Parasitology and Tropical Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • Tam YK; Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
  • Pichyangkul S; Acuitas Therapeutics, Vancouver, BC, V6T 1Z3, Canada.
  • Tsuboi T; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Pardi N; Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
  • Sattabongkot J; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. pnorbert@pennmedicine.upenn.edu.
NPJ Vaccines ; 8(1): 187, 2023 Dec 14.
Article in En | MEDLINE | ID: mdl-38092803
ABSTRACT
Plasmodium vivax (P. vivax) is the major malaria parasite outside of Africa and no vaccine is available against it. A vaccine that interrupts parasite transmission (transmission-blocking vaccine, TBV) is considered highly desirable to reduce the spread of P. vivax and to accelerate its elimination. However, the development of a TBV against this pathogen has been hampered by the inability to culture the parasite as well as the low immunogenicity of the vaccines developed to date. Pvs25 is the most advanced TBV antigen candidate for P. vivax. However, in previous phase I clinical trials, TBV vaccines based on Pvs25 yielded low antibody responses or had unacceptable safety profiles. As the nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine platform proved to be safe and effective in humans, we generated and tested mRNA-LNP vaccines encoding several versions of Pvs25 in mice. We found that in a prime-boost vaccination schedule, all Pvs25 mRNA-LNP vaccines elicited robust antigen-specific antibody responses. Furthermore, when compared with a Pvs25 recombinant protein vaccine formulated with Montanide ISA-51 adjuvant, the full-length Pvs25 mRNA-LNP vaccine induced a stronger and longer-lasting functional immunity. Seven months after the second vaccination, vaccine-induced antibodies retained the ability to fully block P. vivax transmission in direct membrane feeding assays, whereas the blocking activity induced by the protein/ISA-51 vaccine dropped significantly. Taken together, we report on mRNA vaccines targeting P. vivax and demonstrate that Pvs25 mRNA-LNP outperformed an adjuvanted Pvs25 protein vaccine suggesting that it is a promising candidate for further testing in non-human primates.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: NPJ Vaccines Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: NPJ Vaccines Year: 2023 Document type: Article Affiliation country: