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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MDPI AG
2025-01-01
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/34 |
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| author | Ming Xia Pengwei Huang Frank S. Vago Wen Jiang Xi Jiang Ming Tan |
| author_facet | Ming Xia Pengwei Huang Frank S. Vago Wen Jiang Xi Jiang Ming Tan |
| author_sort | Ming Xia |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e8f4550fcdc54cc7ab295481284cb933 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-e8f4550fcdc54cc7ab295481284cb9332025-01-24T13:51:43ZengMDPI AGVaccines2076-393X2025-01-011313410.3390/vaccines13010034A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine CandidateMing Xia0Pengwei Huang1Frank S. Vago2Wen Jiang3Xi Jiang4Ming Tan5Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USADivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USADivision of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USABackground: 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.https://www.mdpi.com/2076-393X/13/1/34norovirus<i>Plasmodium</i>norovirus P particlenanoparticleαTSR domainnanoparticle vaccine |
| spellingShingle | Ming Xia Pengwei Huang Frank S. Vago Wen Jiang Xi Jiang Ming Tan A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate Vaccines norovirus <i>Plasmodium</i> norovirus P particle nanoparticle αTSR domain nanoparticle vaccine |
| title | A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate |
| title_full | A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate |
| title_fullStr | A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate |
| title_full_unstemmed | A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate |
| title_short | A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and <i>Plasmodium</i> as a Combination Vaccine Candidate |
| title_sort | nanoparticle comprising the receptor binding domains of norovirus and i plasmodium i as a combination vaccine candidate |
| topic | norovirus <i>Plasmodium</i> norovirus P particle nanoparticle αTSR domain nanoparticle vaccine |
| url | https://www.mdpi.com/2076-393X/13/1/34 |
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