mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum

Clifford T. Hayashi, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
Yi Cao, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
Leor C. Clark, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
Abhai K. Tripathi, Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21215, USA.
Fidel Zavala, Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21215, USA.
Garima Dwivedi, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
James Knox, Department of Pathology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Mohamad-Gabriel Alameh, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Paulo J. Lin, Acuitas Therapeutics, Vancouver, BC, Canada.
Ying K. Tam, Acuitas Therapeutics, Vancouver, BC, Canada.
Drew Weissman, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nirbhay Kumar, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA. nkumar@gwu.edu.

Document Type

Journal Article

Publication Date

12-1-2022

Journal

NPJ vaccines

Volume

7

Issue

1

DOI

10.1038/s41541-022-00577-8

Abstract

Malaria is a deadly disease responsible for between 550,000 and 627,000 deaths annually. There is a pressing need to develop vaccines focused on malaria elimination. The complex lifecycle of Plasmodium falciparum provides opportunities not only to target the infectious sporozoite stage, introduced by anopheline mosquitoes, but also the sexual stages, which are ingested by mosquitoes during blood feeding, leading to parasite transmission. It is widely recognized that a vaccine targeting multiple stages would induce efficacious transmission reducing immunity. Technological advancements offer new vaccine platforms, such as mRNA-LNPs, which can be used to develop highly effective malarial vaccines. We evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes. Additionally, mice after three and four immunizations with PfCSP mRNA-LNP provided evidence for varying degrees of protection against sporozoite challenge. The comparison of immune responses and stage-specific functional activity induced by each mRNA-LNP vaccine, administered alone or in combination, also supports the development of an effective combination vaccine without any risk of immune interference for targeting malaria parasites at various life cycle stages. A combination of vaccines targeting both the infective stage and sexual/midgut stages is expected to interrupt malaria transmission, which is critical for achieving elimination goals.

Department

Global Health

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