A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and Plasmodium as a Combination Vaccine Candidate.

التفاصيل البيبلوغرافية
العنوان:	A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and Plasmodium as a Combination Vaccine Candidate.
المؤلفون:	Xia, Ming, Huang, Pengwei, Vago, Frank S., Jiang, Wen, Jiang, Xi, Tan, Ming
المصدر:	Vaccines; Jan2025, Vol. 13 Issue 1, p34, 21p
مصطلحات موضوعية:	PROTEIN expression, HEPARAN sulfate proteoglycans, CIRCUMSPOROZOITE protein, COMBINED vaccines, NANOPARTICLES
مستخلص:	Background: Noroviruses, which cause epidemic acute gastroenteritis, and Plasmodium 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 Plasmodium 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 (P24 NP). Methods: We generated a unique P24-αTSR NP by inserting the αTSR domain into a surface loop of the P domain. The P-αTSR fusion proteins were produced in the Escherichia coli expression system and the fusion protein self-assembled into the P24-αTSR NP. Results: The formation of the P24-αTSR NP was demonstrated through gel filtration, electron microscopy, and dynamic light scattering. A 3D structural model of the P24-αTSR NP was constructed, using the known cryo-EM structure of the previously developed P24 NP and P24-VP8* NP as templates. Each P24-αTSR NP consists of a P24 NP core, with 24 surface-exposed αTSR domains that have retained their general conformations and binding function to heparan sulfate proteoglycans. The P24-αTSR NP is immunogenic, eliciting strong antibody responses in mice toward both the norovirus P domain and the αTSR domain of Plasmodium CSP. Notably, sera from mice immunized with the P24-αTSR NP bound strongly to Plasmodium sporozoites and blocked norovirus VLP attachment to their glycan receptors. Conclusion: These data suggest that the P24-αTSR NP may serve as a combination vaccine against both norovirus and Plasmodium parasites. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات:	Complementary Index

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