A Plasmodium berghei sporozoite-based vaccination platform against human malaria
Name
s41541-018-0068-2.pdf
Description
Published version
Size
2.21 MB
Format
Unknown
Checksum (MD5)
34a3835376148ad32e056814881290a3
Author(s)
Mendes, Antonio M.
Machado, Marta
Goncalves-Rosa, Nataniel
Reuling, Isaie J.
Foquet, Lander
Marques, Claudia
Salman, Ahmed M.
Yang, Annie S. P.
Moser, Kara A.
Dwivedi, Ankit
Date Issued
2018
Publisher
Springer Nature
Version
Final published version
Abstract
© 2018, The Author(s). There is a pressing need for safe and highly effective Plasmodium falciparum (Pf) malaria vaccines. The circumsporozoite protein (CS), expressed on sporozoites and during early hepatic stages, is a leading target vaccine candidate, but clinical efficacy has been modest so far. Conversely, whole-sporozoite (WSp) vaccines have consistently shown high levels of sterilizing immunity and constitute a promising approach to effective immunization against malaria. Here, we describe a novel WSp malaria vaccine that employs transgenic sporozoites of rodent P. berghei (Pb) parasites as cross-species immunizing agents and as platforms for expression and delivery of PfCS (PbVac). We show that both wild-type Pb and PbVac sporozoites unabatedly infect and develop in human hepatocytes while unable to establish an infection in human red blood cells. In a rabbit model, similarly susceptible to Pb hepatic but not blood infection, we show that PbVac elicits cross-species cellular immune responses, as well as PfCS-specific antibodies that efficiently inhibit Pf sporozoite liver invasion in human hepatocytes and in mice with humanized livers. Thus, PbVac is safe and induces functional immune responses in preclinical studies, warranting clinical testing and development.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41541-018-0068-2
