A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate
Background: Noroviruses, which cause epidemic acute gastroenteritis, and <i>Plasmodium</i> parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CS...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/34 |
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| Summary: | Background: Noroviruses, which cause epidemic acute gastroenteritis, and <i>Plasmodium</i> parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of <i>Plasmodium</i> sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P<sub>24</sub> NP). Methods: We generated a unique P<sub>24</sub>-αTSR NP by inserting the αTSR domain into a surface loop of the P domain. The P-αTSR fusion proteins were produced in the <i>Escherichia coli</i> expression system and the fusion protein self-assembled into the P<sub>24</sub>-αTSR NP. Results: The formation of the P<sub>24</sub>-αTSR NP was demonstrated through gel filtration, electron microscopy, and dynamic light scattering. A 3D structural model of the P<sub>24</sub>-αTSR NP was constructed, using the known cryo-EM structure of the previously developed P<sub>24</sub> NP and P<sub>24</sub>-VP8* NP as templates. Each P<sub>24</sub>-αTSR NP consists of a P<sub>24</sub> NP core, with 24 surface-exposed αTSR domains that have retained their general conformations and binding function to heparan sulfate proteoglycans. The P<sub>24</sub>-αTSR NP is immunogenic, eliciting strong antibody responses in mice toward both the norovirus P domain and the αTSR domain of <i>Plasmodium</i> CSP. Notably, sera from mice immunized with the P<sub>24</sub>-αTSR NP bound strongly to <i>Plasmodium</i> sporozoites and blocked norovirus VLP attachment to their glycan receptors. Conclusion: These data suggest that the P<sub>24</sub>-αTSR NP may serve as a combination vaccine against both norovirus and <i>Plasmodium</i> parasites. |
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| ISSN: | 2076-393X |