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Theranostics 2020; 10(13):5704-5718. doi:10.7150/thno.42494 This issue Cite

Research Paper

A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection

Xiao Zhang1,*, Bingchun Zhao1,4,*, Mingmei Ding5, Shuo Song6, Yinfeng Kang1, Yang Yu1, Miao Xu1, Tong Xiang1, Ling Gao1, Qisheng Feng1, Qinjian Zhao2✉, Mu-Sheng Zeng1✉, Claude Krummenacher3, Yi-Xin Zeng1✉

1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, PR China
2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, Fujian, PR China
3. Department of Biological Sciences and Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ, United States
4. Present address: Vaccine Research Center, National Institute of Allergy and Infection Diseases, National Institutes of Health, Bethesda, MD, United States
5. School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, PR China
6. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen, China
* These authors contributed equally to this work.

✉ Corresponding authors: Qinjian Zhao, School of Public Health, Xiamen University, Xiamen, Fujian, 361005, PR China, qinjian_zhaoedu.cn. Mu-Sheng Zeng, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, PR China, zengmsho More

Citation:
Zhang X, Zhao B, Ding M, Song S, Kang Y, Yu Y, Xu M, Xiang T, Gao L, Feng Q, Zhao Q, Zeng MS, Krummenacher C, Zeng YX. A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection. Theranostics 2020; 10(13):5704-5718. doi:10.7150/thno.42494. https://www.thno.org/v10p5704.htm
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Abstract

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Rationale: Epstein-Barr virus (EBV) is the causative pathogen for infectious mononucleosis and many kinds of malignancies including several lymphomas such as Hodgkin's lymphoma, Burkitt's lymphoma and NK/T cell lymphoma as well as carcinomas such as nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBV-GC). However, to date no available prophylactic vaccine was launched to the market for clinical use.

Methods: To develop a novel vaccine candidate to prevent EBV infection and diseases, we designed chimeric virus-like particles (VLPs) based on the hepatitis B core antigen (HBc149). Various VLPs were engineered to present combinations of three peptides derived from the receptor binding domain of EBV gp350. All the chimeric virus-like particles were injected into Balb/C mice for immunogenicity evaluation. Neutralizing titer of mice sera were detected using an in vitro cell model.

Results: All chimeric HBc149 proteins self-assembled into VLPs with gp350 epitopes displayed on the surface of spherical particles. Interestingly, the different orders of the three epitopes in the chimeric proteins induced different immune responses in mice. Two constructs (149-3A and 149-3B) induced high serum titer against the receptor-binding domain of gp350. Most importantly, these two VLPs elicited neutralizing antibodies in immunized mice, which efficiently blocked EBV infection in cell culture. Competition analysis showed that sera from these mice contained antibodies to a major neutralizing epitope recognized by the strong neutralizing mAb 72A1.

Conclusion: Our data demonstrate that HBc149 chimeric VLPs provide a valuable platform to present EBV gp350 antigens and offer a robust basis for the development of peptide-based candidate vaccines against EBV.

Keywords: Epstein-Barr virus, Envelope glycoprotein, gp350, Conserved epitope peptide, HBc149, Chimeric virus-like particle, Neutralizing antibody.

Citation styles

APA
Zhang, X., Zhao, B., Ding, M., Song, S., Kang, Y., Yu, Y., Xu, M., Xiang, T., Gao, L., Feng, Q., Zhao, Q., Zeng, M.S., Krummenacher, C., Zeng, Y.X. (2020). A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection. Theranostics, 10(13), 5704-5718. https://doi.org/10.7150/thno.42494.

ACS
Zhang, X.; Zhao, B.; Ding, M.; Song, S.; Kang, Y.; Yu, Y.; Xu, M.; Xiang, T.; Gao, L.; Feng, Q.; Zhao, Q.; Zeng, M.S.; Krummenacher, C.; Zeng, Y.X. A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection. Theranostics 2020, 10 (13), 5704-5718. DOI: 10.7150/thno.42494.

NLM
Zhang X, Zhao B, Ding M, Song S, Kang Y, Yu Y, Xu M, Xiang T, Gao L, Feng Q, Zhao Q, Zeng MS, Krummenacher C, Zeng YX. A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection. Theranostics 2020; 10(13):5704-5718. doi:10.7150/thno.42494. https://www.thno.org/v10p5704.htm

CSE
Zhang X, Zhao B, Ding M, Song S, Kang Y, Yu Y, Xu M, Xiang T, Gao L, Feng Q, Zhao Q, Zeng MS, Krummenacher C, Zeng YX. 2020. A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection. Theranostics. 10(13):5704-5718.

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