Pseudovirus Nanoparticles Displaying Plasmodium Circumsporozoite Proteins Elicited High Titers of Sporozoite-Binding Antibody

Autor: Ming Xia, Pengwei Huang, Frank Vago, Wen Jiang, Ming Tan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Vaccines, Vol 11, Iss 11, p 1650 (2023)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines11111650
Popis: Background: malaria caused by Plasmodium parasites remains a public health threat. The circumsporozoite proteins (CSPs) of Plasmodium sporozoite play a key role in Plasmodium infection, serving as an excellent vaccine target. Methods: using a self-assembled S60 nanoparticle platform, we generated pseudovirus nanoparticles (PVNPs) displaying CSPs, named S-CSPs, for enhanced immunogenicity. Results: purified Hisx6-tagged or tag-free S-CSPs self-assembled into PVNPs that consist of a norovirus S60 inner shell and multiple surface-displayed CSPs. The majority of the PVNPs measured ~27 nm with some size variations, and their three-dimensional structure was modeled. The PVNP-displayed CSPs retained their glycan receptor-binding function. A mouse immunization study showed that PVNPs induced a high antibody response against CSP antigens and the PVNP-immunized mouse sera stained the CSPs of Plasmodium sporozoites at high titer. Conclusions and discussion: the PVNP-displayed CSPs retain their authentic antigenic feature and receptor-binding function. The CSP-specific antibody elicited by the S-CSP PVNPs binds original CSPs and potentially inhibits the attachment of Plasmodium sporozoites to their host cells, a key step for liver invasion by the sporozoites. Thus, S-CSP PVNPs may be an excellent vaccine candidate against malaria caused by Plasmodium parasites.
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