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Volume 39 Issue 5
October 2024

    . doi: 10.1016/j.virs.2024.08.005
    Citation: Lu Zhang, Siyu Tian, Jun Dai, Yuanyuan Li, Yu Zhou, Yan Li, Jiao Xu, Shuyun Liu, Zhiwei Lin, Zhaoyong Zhang, Jiantao Chen, Peilan Wei, Jingxian Zhao, Jing Jin, Yanqun Wang, Jincun Zhao. Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants .VIROLOGICA SINICA, 2024, 39(5) : 836-839.  http://dx.doi.org/10.1016/j.virs.2024.08.005
    shu

    新冠三价病毒样颗粒疫苗对XBB.1和BA.2.86等变异株具有广谱中和保护特性

    cstr: 32224.14.j.virs.2024.08.005

    • a. 呼吸疾病全国重点实验室、海关总署公共卫生安全中心实验室、广州海关技术中心;

    • b. 广州派诺生物技术有限公司;

    • c. 呼吸疾病全国重点实验室, 国家呼吸系统疾病临床医学研究中心, 广州呼吸健康研究所, 广州医科大学附属第一医院;

    • d. 广州国家实验室;

    • e. 广州医科大学第二附属医院, 临床实验室医学部;

    • f. 上海科技大学生命科学与技术学院, 上海科技大学免疫化学研究所;

    • g. 深圳市第三人民医院, 国家感染性疾病临床医学研究中心, 肝病研究所;南方科技大学医学院第二附属医院

    • SARS-CoV-2的Omicron亚分支XBB.1、EG.5和JN.1等在全球范围内先后传播，相较于其他Omicron变种具有更强的传播。然而早期的BA.2或BA.5等二价疫苗作为第二代疫苗代表，对新出现的XBB.1或EG.5及其分支变异株均未能产生强效的中和反应。XBB.1，EG.5, JN.1及其亚分支已迅速成为主要的SARS-CoV-2毒株，开发针对新出现的SARS-CoV-2变异株的更新疫苗至关重要。
      本研究中我们开发了一种特殊的三价SARS-CoV-2病毒样颗粒（包括WT、BQ.1.1和XBB.1的RBD）疫苗RBDV14M，通过基因融合和linker串联表达，展示在新型VLP载体表面，结合自备佐剂，成功制备了RBDV14M疫苗。小鼠上免疫RBDV14M疫苗可诱导针对新出现的SARS-CoV-2变异株XBB.1、BQ.1.1、EG.5和BA.2.86的优越、广谱的中和抗体反应，对于最新毒株，中和逃逸程度明显降低。体内研究还表明，RBDV14M疫苗接种能有效保护小鼠免受XBB.1和BQ.1.1变异株的攻击，新冠疫苗不断更新迭代，新载体、新策略的优化可以增强广谱疫苗的保护效果，本研究表明该VLP疫苗可能是一个有效且成功的SARS-CoV-2广谱疫苗候选者。

    Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants

    • a. State Key Laboratory of Respiratory Disease, Public Health Safety Center Laboratory of General Administration of Customs, Guangzhou Customs Technology Center, Guangzhou, Guangdong, 510182, China;

    • b. Patronus Biotech Co. Ltd., Guangzhou, 510182, China;

    • c. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, China;

    • d. Guangzhou National Laboratory, Guangzhou, Guangdong, 510182, China;

    • e. Clinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, China;

    • f. Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China;

    • g. Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital;The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, 518000, China

    • Highlights
      1. RBDs of the WT, BQ.1.1 and XBB.1 variants were genetically fused and displayed on the VLP to create RBDV14 ​M.
      2. RBDV14 ​M can induce superior antibody responses against the newly emerged SARS-CoV-2 variants XBB.1, EG.5 and BA.2.86.
      3. RBDV14 ​M is one of the few existing next-generation vaccine candidates that utilize virus-like particle platform.
    • 加载中

      1. Faraone, J. N., Qu, P., Goodarzi, N., Zheng, Y. M., Carlin, C., Saif, L. J., Oltz, E. M., Xu, K., Jones, D., Gumina, R. J. et al., 2023. Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3. Emerg. Microb. Infect.12, 2270069.

      2. Hu, Y., Zou, J., Kurhade, C., Deng, X., Chang, H. C., Kim, D. K., Shi, P. Y., Ren, P., Xie, X., 2023. Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1. Emerg. Microb. Infect. 12, 2271089.

      3. Lasrado, N., Collier, A. Y., Hachmann, N. P., Miller, J., Rowe, M., Schonberg, E. D., Rodrigues, S. L., LaPiana, A., Patio, R. C., Anand, T. et al., 2023. Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86. Vaccine. 41, 6904-6909.

      4. Li, Y., Zhang, Y., Zhou, Y., Li, Y., Xu, J., Ai, Y., Xu, L., Xiao, X., Zhang, B., Jin, J., 2023. An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques. Signal Transduct. Targeted Ther. 8, 173.

      5. Tamura, T., Ito, J., Uriu, K., Zahradnik, J., Kida, I., Anraku, Y., Nasser, H., Shofa, M., Oda, Y., Lytras, S. et al., 2023. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. Nat. Commun. 14, 2800.

      6. Tan, C. W., Chia, W. N., Young, B. E., Zhu, F., Lim, B. L., Sia, W.R., Thein, T. L., Chen, M. I., Leo, Y. S., Lye, D. C. et al., 2021. Pan-sarbecovirus neutralizing antibodies in BNT162b2-immunized SARS-CoV-1 survivors. N. Engl. J. Med. 385, 1401-1406.

      7. Wang, Q., Guo, Y., Zhang, R. M., Ho, J., Mohri, H., Valdez, R., Manthei, D. M., Gordon, A., Liu, L., Ho, D. D., 2023a. Antibody neutralisation of emerging SARS-CoV-2 subvariants: EG.5.1 and XBC.1.6. Lancet Infect. Dis. 23, e397-e398.

      8. Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A. D., Liu, M., Wang, M., Yu, J. et al., 2023b. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 186, 279-286.

      9. Wang, Q., Guo, Y., Liu, L., Schwanz, L. T., Li, Z., Nair, M. S., Ho, J., Zhang, R. M., Iketani, S., Yu, J. et al., 2023c. Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike. Nature. 624, 639-644.

      10. Ward, B. J., Gobeil, P., Seguin, A., Atkins, J., Boulay, I., Charbonneau, P. Y., Couture, M., D'Aoust, M. A., Dhaliwall, J., Finkle, C. et al., 2021. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat. Med. 27, 1071-1078.

      11. Zou, J., Kurhade, C., Patel, S., Kitchin, N., Tompkins, K., Cutler, M., Cooper, D., Yang, Q., Cai, H., Muik, A. et al., 2023. Neutralization of BA.4-BA.5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with bivalent vaccine. N. Engl. J. Med. 388, 854-857.

    • 加载中

    • Electronic Supplementary Material

      10.1016j.virs.2024.08.005-ESM.docx

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      Trivalent SARS-CoV-2 virus-like particle vaccines exhibit broad-spectrum neutralization and protection against XBB.1 and BA.2.86 variants

        Corresponding author: Jingxian Zhao, zhaojincun@gird.cn
        Corresponding author: Jing Jin, jinjing@luye.com
        Corresponding author: Yanqun Wang, wangyanqun@gird.cn
        Corresponding author: Jincun Zhao, zhaojingxian@gird.cn
      • a. State Key Laboratory of Respiratory Disease, Public Health Safety Center Laboratory of General Administration of Customs, Guangzhou Customs Technology Center, Guangzhou, Guangdong, 510182, China;
      • b. Patronus Biotech Co. Ltd., Guangzhou, 510182, China;
      • c. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, China;
      • d. Guangzhou National Laboratory, Guangzhou, Guangdong, 510182, China;
      • e. Clinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510182, China;
      • f. Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China;
      • g. Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital;The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, 518000, China
      • Received Date: 30 March 2024
      • Accepted Date: 13 August 2024

      Abstract: Highlights
      1. RBDs of the WT, BQ.1.1 and XBB.1 variants were genetically fused and displayed on the VLP to create RBDV14 ​M.
      2. RBDV14 ​M can induce superior antibody responses against the newly emerged SARS-CoV-2 variants XBB.1, EG.5 and BA.2.86.
      3. RBDV14 ​M is one of the few existing next-generation vaccine candidates that utilize virus-like particle platform.

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