Pseudovirus Nanoparticles Displaying <i>Plasmodium</i> Circumsporozoite Proteins Elicited High Titers of Sporozoite-Binding Antibody

oleh: Ming Xia, Pengwei Huang, Frank Vago, Wen Jiang, Ming Tan

Format: Article
Diterbitkan: MDPI AG 2023-10-01

Deskripsi

Background: malaria caused by <i>Plasmodium</i> parasites remains a public health threat. The circumsporozoite proteins (CSPs) of <i>Plasmodium</i> sporozoite play a key role in <i>Plasmodium</i> infection, serving as an excellent vaccine target. Methods: using a self-assembled S<sub>60</sub> 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 S<sub>60</sub> 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 <i>Plasmodium</i> 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 <i>Plasmodium</i> 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 <i>Plasmodium</i> parasites.