Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells
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The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-alpha in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-alpha. Further study indicated that IFN-gamma+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV.
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VLPs are nanoscale structures made up of one or more different molecules with the ability to self-assemble, mimicking the form and size of a virus particle, but lacking viral genetic material and being non-infectious.
“VLPs are nanoscale structures made up of one or more different molecules with the ability to self-assemble, mimicking the form and size of a virus particle, but lacking the viral genetic material and being non-infectious [80].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [80]
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Khan, M., Musazzi, U. M., Manellari, S., Mouawad, N., Damiano, G., Rinaldi, R., Raucci, A., Costantino, S., Paneni, F., Minghetti, P., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107847 · Cited by 15 · see citing works
Mi, Y., Liang, L., Xu, K., Li, Q., Wang, W., Dang, W., Deng, J., Zhi, Y., Li, X., & Tan, J. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.986350 · Cited by 13 · see citing works
Attacking the Intruder at the Gate: Prospects of Mucosal Anti SARS-CoV-2 Vaccines
Karczmarzyk, K., & Kęsik-Brodacka, M. (2022) · Pathogens · doi:10.3390/pathogens11020117 · Cited by 12 · see citing works
Sebastião, A. I., Mateus, D., Carrascal, M. A., Sousa, C., Cortes, L., Bachmann, M. F., do Carmo, A., Matos, A. M., Sales, M. G. F., & Cruz, M. T. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15030825 · Cited by 11 · see citing works
Jha, K., Jaishwal, P., Yadav, T. P., & Singh, S. P. (2024) · Biophysical Chemistry · doi:10.1016/j.bpc.2024.107375 · Cited by 10 · see citing works
Costa, G. L., & Sautto, G. A. (2025) · Expert Review of Vaccines · doi:10.1080/14760584.2025.2452955 · Cited by 8 · see citing works
Hu, X., Wang, Z., Wang, S., Sun, H., Feng, N., Li, E., Xia, X., Hu, G., & Yan, F. (2025) · Transboundary and Emerging Diseases · doi:10.1155/tbed/2014296 · Cited by 9 · see citing works
Su, S., Shen, X., Shi, X., Li, X., Chen, J., Yang, W., Sun, M., Tang, Y., Wang, H., Wang, S., et al. (2024) · Frontiers in Veterinary Science · doi:10.3389/fvets.2024.1460973 · Cited by 7 · see citing works
Self-citationImmunogenicity of the spike glycoprotein of Bat SARS-like coronavirus
Hou, Y.-X., Peng, C., Han, Z., Zhou, P., Chen, J., & Shi, Z. (2010) · Virologica Sinica · doi:10.1007/s12250-010-3096-2 · Cited by 6 · see citing works
Self-citationNeef, A., Nath, B. K., Das, T., Luque, D., Forwood, J. K., Raidal, S. R., & Das, S. (2024) · Veterinary Research Communications · doi:10.1007/s11259-023-10290-z · Cited by 5 · see citing works
Mammalian cells-based platforms for the generation of SARS-CoV-2 virus-like particles
Elfayres, G., Paswan, R. R., Sika, L., Girard, M.-P., Khalfi, S., Letanneur, C., Milette, K., Singh, A., Kobinger, G., & Berthoux, L. (2023) · Journal of Virological Methods · doi:10.1016/j.jviromet.2023.114835 · Cited by 4 · see citing works
Virus-like particles: Bridging immunization and precision drug delivery
Gupta, J., Tiwari, P., & Kumar, R. (2026) · Gene · doi:10.1016/j.gene.2026.150208 · Cited by 3 · see citing works
Characterization of alfalfa mosaic virus capsid protein using Cryo-EM
Jeong, H., Park, Y., Song, S., Min, K., Woo, J., Lee, Y., Sohn, E., & Lee, S. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.04.060 · Cited by 3 · see citing works
VLP (Virus-Like Particles) Vaccines - Current Knowledge and Future Directions
Meghana, P., Jayasri, M. A., & Suthindhiran, K. (2025) · Brazilian Archives of Biology and Technology · doi:10.1590/1678-4324-2025240942 · Cited by 2 · see citing works
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Anoushirvani, A. A., Moshfeghi, K., Rafiee, M., & Bakhshi, S. (2013)
Examples of studies using our ELISPOT assays
Bai, B., Hu, H., Zhou, P., Shi, Z., Meng, J., Lu, B., Huang, Y., Mao, P., & Wang, H. (2011)
Self-citationUvarova, E. A., Belavin, P. A., & Дейнеко, Е. В. (2022) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-22-39
Emerging role of vaccines in glioblastoma treatment
Li, J., & Li, X. (2023) · Highlights in Science Engineering and Technology · doi:10.54097/hset.v36i.6283
Role of Nanoparticle Formulation for the Combination Delivery of Multiple Antigens
Lahane, G. P., Ghatage, T., Venkadakrishnan, J., Dube, T., Arondekar, D., Kumar, R. R., Dhar, A., & Bhat, A. (2024) · Springer eBooks · doi:10.1007/978-981-96-0397-8_7
Trends in the development of nanovaccines against swine diseases
León-Montoya, H., & Angulo, C. (2025) · Vaccine · doi:10.1016/j.vaccine.2025.127491
FAIRsharing record for: Virus Particle Explorer
FAIRsharing Team, & McQuilton, P. (2022) · FAIRsharing.org · doi:10.25504/fairsharing.45e0f5
- Authors
- Bai, B., Hu, Q., Hu, H., Zhou, P., Shi, Z., Meng, J., Lu, B., Huang, Y., Mao, P., & Wang, H.
- Affiliations
- Chinese Academy of Sciences (CN)
- National Institute for Communicable Disease Control and Prevention (CN)
- Corresponding author
- Wang, Hanzhong
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-07-16
- Volume
- 3
- Issue
- 7
- Pages
- e2685
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2441860
- OpenAlex
- W2046789235
- Cited by
- 59
- References
- 50
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 5 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Sciences (KSCX1-YW-R-07)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- SARS-like coronaviruses, SARS coronavirus, virus-like particles, recombinant baculovirus, spike protein, envelope protein, membrane proteins, dendritic cell activation, costimulatory molecules, cytokine production, interleukin-6, TNF-α, IL-10, CD4+ T cell responses, DNA vaccine, bat coronaviruses, vaccine development
- MeSH terms
- Cell Differentiation, Dendritic Cells, Humans, Immune System, Interferon-gamma, Leukocytes, Mononuclear, Membrane Proteins, Phenotype, Plasmids, CD4-Positive T-Lymphocytes, Interleukin-4, Cytokines, Baculoviridae, Th1 Cells, Severe acute respiratory syndrome-related coronavirus
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