A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection
BackgroundEpstein–Barr virus (EBV) is a significant global public health concern because of its association with various malignancies and autoimmune diseases. Over 90% of the global population is chronically infected with EBV, impacting numerous cancer-related cases annually. However, none of the ef...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530364/full |
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| author | Ping Li Ping Li Ziyi Jiang Jingjing Shi Haochuan Sha Zihang Yu Yan Zhao Sanyang Han Lan Ma Lan Ma Lan Ma |
| author_facet | Ping Li Ping Li Ziyi Jiang Jingjing Shi Haochuan Sha Zihang Yu Yan Zhao Sanyang Han Lan Ma Lan Ma Lan Ma |
| author_sort | Ping Li |
| collection | DOAJ |
| description | BackgroundEpstein–Barr virus (EBV) is a significant global public health concern because of its association with various malignancies and autoimmune diseases. Over 90% of the global population is chronically infected with EBV, impacting numerous cancer-related cases annually. However, none of the effective prophylactic vaccines against EBV is approved at present.MethodsIn this study, we developed a novel vaccine candidate based on epitope peptides from the receptor-binding domain of EBV-encoded gp350 glycoprotein to prevent EBV infection. These epitope peptides detected a binding capability with host cells were then fused by flexibility linkers and expressed in Escherichia coli to reduce the unnecessary glycan modifications to simulate their free-glycan status. The fused recombinant protein (L350) was displayed on the surface of ferritin-based nanoparticle. The immunogenicity of the L350–ferritin nanoparticle was evaluated in Balb/c mice, and the neutralizing titers of sera from immunized mice were detected by means of an infection blocking assay in an in vitro cell model.ResultsAll the five epitope peptides could bind to AKATA cells, and their fused recombinant protein (L350) was successfully presented on the surface of self-assembled ferritin nanoparticles. Sera from the L350–ferritin nanoparticle-immunized mice showed high titers of both L350 protein-specific and gp350D123 protein-specific antibodies, and sera from gp350D123 protein-immunized mice could also recognize L350 protein well. Most importantly, the L350–ferritin nanoparticle induced efficient neutralizing antibodies to block EBV-GFP infection in AKATA cells and also constructed a strong antigen-specific B-cell memory in immunized mice. Moreover, histopathological changes of main tissues from all vaccinated mice were not observed.ConclusionThese data indicate that the L350–ferritin nanoparticle vaccine candidate has considerable potential application in preventing EBV infection and provides a promising basis for developing prophylactic EBV vaccines. |
| format | Article |
| id | doaj-art-f70313e4b5644650825c890a7f4d51ad |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f70313e4b5644650825c890a7f4d51ad2025-02-04T09:43:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15303641530364A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infectionPing Li0Ping Li1Ziyi Jiang2Jingjing Shi3Haochuan Sha4Zihang Yu5Yan Zhao6Sanyang Han7Lan Ma8Lan Ma9Lan Ma10Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaInstitute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaCollege of International Education, Henan University of Technology, Zhengzhou, ChinaInstitute of Bio-Architeture and Bio-Interactions, Shenzhen Medical Academy of Research and Translation, Shenzhen, ChinaInstitute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaInstitute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaInstitute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, ChinaState Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, ChinaBackgroundEpstein–Barr virus (EBV) is a significant global public health concern because of its association with various malignancies and autoimmune diseases. Over 90% of the global population is chronically infected with EBV, impacting numerous cancer-related cases annually. However, none of the effective prophylactic vaccines against EBV is approved at present.MethodsIn this study, we developed a novel vaccine candidate based on epitope peptides from the receptor-binding domain of EBV-encoded gp350 glycoprotein to prevent EBV infection. These epitope peptides detected a binding capability with host cells were then fused by flexibility linkers and expressed in Escherichia coli to reduce the unnecessary glycan modifications to simulate their free-glycan status. The fused recombinant protein (L350) was displayed on the surface of ferritin-based nanoparticle. The immunogenicity of the L350–ferritin nanoparticle was evaluated in Balb/c mice, and the neutralizing titers of sera from immunized mice were detected by means of an infection blocking assay in an in vitro cell model.ResultsAll the five epitope peptides could bind to AKATA cells, and their fused recombinant protein (L350) was successfully presented on the surface of self-assembled ferritin nanoparticles. Sera from the L350–ferritin nanoparticle-immunized mice showed high titers of both L350 protein-specific and gp350D123 protein-specific antibodies, and sera from gp350D123 protein-immunized mice could also recognize L350 protein well. Most importantly, the L350–ferritin nanoparticle induced efficient neutralizing antibodies to block EBV-GFP infection in AKATA cells and also constructed a strong antigen-specific B-cell memory in immunized mice. Moreover, histopathological changes of main tissues from all vaccinated mice were not observed.ConclusionThese data indicate that the L350–ferritin nanoparticle vaccine candidate has considerable potential application in preventing EBV infection and provides a promising basis for developing prophylactic EBV vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530364/fullEpstein-Barr virus (EBV)vaccineepitopeferritinnanoparticle |
| spellingShingle | Ping Li Ping Li Ziyi Jiang Jingjing Shi Haochuan Sha Zihang Yu Yan Zhao Sanyang Han Lan Ma Lan Ma Lan Ma A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection Frontiers in Immunology Epstein-Barr virus (EBV) vaccine epitope ferritin nanoparticle |
| title | A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection |
| title_full | A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection |
| title_fullStr | A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection |
| title_full_unstemmed | A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection |
| title_short | A self-assembled nanoparticle vaccine elicits effective neutralizing antibody response against EBV infection |
| title_sort | self assembled nanoparticle vaccine elicits effective neutralizing antibody response against ebv infection |
| topic | Epstein-Barr virus (EBV) vaccine epitope ferritin nanoparticle |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1530364/full |
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