Chimeric virus-like-particle vaccines for malaria using mRNA constructs for delivery

Francisco Jose MARTINEZ BLAZQUEZ (Biologie de Plasmodium et Vaccins, Institut Pasteur, Paris)

12 décembre 2024

Séminaire

Infos pratiques

12:00 - 13:00

Salle Rosalind Franklin

Professionnel de recherche

Accès mobilité réduite

Malaria still poses a threat to public health in tropical and sub-tropical countries with 250 million cases and 608 thousands deaths reported in year 2022 (1). The first generation of malaria vaccines, RTS,S and R21, are based on virus-like particles (VLPs) consisting of the Plasmodium falciparum (Pf) cirmcumsporozoite protein (PfCSP) fused to the surface antigen of Hepatitis B virus (HBsAg). RTS,S and Rv21 have recently being licensed and showed an efficacy of 40% (2) and 70% (3), respectively. Even though these studies have validated PfCSP as a vaccine candidate for malaria, there is a need for more effective vaccines (4). In addition, P. vivax (Pv) infection is more prevalent in the world outside Africa (5) and yet, there is no licensed vaccine for P. vivax. In this study, we have shown that PfCSP or PvCSP fused with HBsAg and delivered by mRNA secretes chimeric VLPs in HEK293 cells. Importantly, immunization with mRNA encoding these PfCSP or PvCSP fusions elicits protent antibody responses that protects mice against infection of transgenic P. berghei sporozoites expressing PfCSP or PvCSP. Therefore, these studies demonstrated it is possible to use mRNA constructs based on HBsAg fusions with malaria parasite antigens to develop vaccines for P. vivax and P. falciparum malaria.

Paris Post-docs seminar series.

References

World Health Organization C. World malaria report 2023.
WHO. The RTS,S Malaria Vaccine [Internet]. Available from: https://www.who.int/multi-media/details/the-rts-s-malaria-vaccinev2
Datoo MS, Natama HM, Somé A, Bellamy D, Traoré O, Rouamba T, et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. The Lancet Infectious Diseases. 2022 Dec;22(12):1728–36.
WHO. WHO review of malaria vaccine clinical development [Internet]. 2022. Available from: https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/who-review-of-malaria-vaccine-clinical-development
Battle KE, Lucas TCD, Nguyen M, Howes RE, Nandi AK, Twohig KA, et al. Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000–17: a spatial and temporal modelling study. The Lancet. 2019 Jul;394(10195):332–43.

Additional publications

Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, Diouf A, Martinez FJ, Nielsen CM, Lias AM, King LD, Edwards NJ, Greenwood NM. Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection. Science translational medicine. 2023 Jul 12;15(704):eadf1782.
Martinez FJ, White M, Guillotte-Blisnick M, Huon C, Boucharlat A, Agou F, England P, Popovici J, Hou MM, Silk SE, Barrett JR. PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial. npj Vaccines. 2024 Jan 6;9(1):10.

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