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Volume 39 Issue 1
February 2024

    . doi: 10.1016/j.virs.2023.11.007
    Citation: Fan Shen, Chun Liang, Cui-Xian Yang, Ying Lu, An-Qi Li, Ying Duan, Mi Zhang, Ren-Rong Tian, Xing-Qi Dong, Yong-Tang Zheng, Wei Pang. SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants .VIROLOGICA SINICA, 2024, 39(1) : 173-176.  http://dx.doi.org/10.1016/j.virs.2023.11.007
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    接种灭活疫苗后早期新冠病毒突破性感染者体内产生了极低滴度的针对当前奥密克戎XBB各种突变株的中和抗体

    • a. 中国科学院昆明动物研究所;

    • b. 中国科学院大学;

    • c. 云南省传染病医院

    • 中国人群大多数都接种过新冠病毒灭活疫苗，但其中仍有相当一部分人在过去三年中还被新冠病毒感染。最近奥密克戎（Omicron） XBB突变株及其子代谱系已在我国流行，因此，急需了解此类人群对这些流行株的免疫保护水平。在本研究中，我们从云南省收集了91份曾经感染SARS-CoV-2原型株、Delta、Omicron BA.1或Omicron BA.5突变株的康复者血清样本，用基于VSV骨架的假病毒评估了它们针对当前流行的Omicron BF.7、BQ.1、BQ.1.1、XBB、XBB.1和XBB.1.5突变株的的中和活性。结果发现：（1）在未接种过疫苗和接种两剂灭活疫苗后，再被新冠病毒原始株、Delta株或BA.1株感染的人群中，其恢复期血清几乎检测不到针对当前这些Omicron流行株的中和抗体；（2）在接种三剂灭活疫苗后，再被BA.1或BA.5株感染的人群中，其恢复期血清针对当前Omicron变异株的中和抗体滴度升高；并且，相比BA.1株，BA.5株感染诱导了较高滴度的中和抗体；（3）在检测的所有恢复期血清中，都发现针对XBB、XBB.1和XBB.1.5的中和抗体比针对BF.7、BQ.1和BQ.1.1的中和抗体滴度低。本研究表明：在接种新冠病毒灭活疫苗后，再被早期流行的新冠病毒株感染的人群体内，尚未产生足够的交叉中和抗体，以抵御当前流行的Omicron新型突变株的再次感染。因此，此类人群需要加强个人防护；同时，也提示进一步研发新型广谱疫苗的必要性。

    SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

    • a. Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China;

    • b. University of Chinese Academy of Sciences, Beijing, 100049, China;

    • c. Yunnan Provincial Infectious Disease Hospital, Kunming, 650399, China;

    • d. Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China

    • Highlights
      1. Inactivated vaccine breakthrough infection with ancestral or Delta variant induced nearly undetectable nAbs against XBB variants.
      2. Inactivated vaccine breakthrough infection with Omicron BA.1 or BA.5 evoked very weak nAbs against XBB variants.
      3. BA.5 infection induced higher nAbs against XBB variants than BA.1 infection.
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      1. Arunachalam, P. S., Lai, L., Samaha, H., Feng, Y., Hu, M., Hui, H. S., Wali, B., Ellis, M., Davis-Gardner, M. E., Huerta, C., Bechnak, K., Bechnak, S., Lee, M., Litvack, M. B., Losada, C., Grifoni, A., Sette, A., Zarnitsyna, V. I., Rouphael, N., Suthar, M. S., Pulendran, B., 2023. Durability of immune responses to mRNA booster vaccination against COVID-19. J Clin Invest, 133, e167955.

      2. Devasundaram, S., Terpos, E., Rosati, M., Ntanasis-Stathopoulos, I., Bear, J., Burns, R., Skourti, S., Malandrakis, P., Trougakos, I. P., Dimopoulos, M. A., Pavlakis, G. N., Felber, B. K., 2023. XBB.1.5 neutralizing antibodies upon bivalent COVID-19 vaccination are similar to XBB but lower than BQ.1.1. Am J Hematol, 98, E123-E126.

      3. Hoffmann, M., Arora, P., Nehlmeier, I., Kempf, A., Cossmann, A., Schulz, S. R., Morillas Ramos, G., Manthey, L. A., Jäck, H. M., Behrens, G. M. N., Pöhlmann, S., 2023. Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5. Cell Mol Immunol, 20, 419-422.

      4. Kaku, Y., Kosugi, Y., Uriu, K., Ito, J., Hinay, A. A., Jr, Kuramochi, J., Sadamasu, K., Yoshimura, K., Asakura, H., Nagashima, M., Genotype to Phenotype Japan (G2P-Japan) Consortium, Sato, K., 2023. Antiviral efficacy of the SARS-CoV-2 XBB breakthrough infection sera against omicron subvariants including EG.5. Lancet Infect Dis, 23, e395-e396.

      5. Ma, K. C., Shirk, P., Lambrou, A. S., Hassell, N., Zheng, X. Y., Payne, A. B., Ali, A. R., Batra, D., Caravas, J., Chau, R., Cook, P. W., Howard, D., Kovacs, N. A., Lacek, K. A., Lee, J. S., MacCannell, D. R., Malapati, L., Mathew, S., Mittal, N., Nagilla, R. R., Parikh, R., Paul, P., Rambo-Martin, B.L., Shepard, S.S., Sheth, M., Wentworth, D. E., Winn, A., Hall, A.J., Silk, B.J., Thornburg, N., Kondor, R., Scobie, HM., Paden, C. R., 2023. Genomic Surveillance for SARS-CoV-2 Variants: Circulation of Omicron Lineages - United States, January 2022-May 2023. MMWR Morb Mortal Wkly Rep, 72, 651-656.

      6. Schmidt, F., Weisblum, Y., Muecksch, F., Hoffmann, H. H., Michailidis, E., Lorenzi, J. C. C., Mendoza, P., Rutkowska, M., Bednarski, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Caskey, M., Robbiani, D. F., Nussenzweig, M. C., Rice, C. M., Hatziioannou, T., Bieniasz, P. D., 2020. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J Exp Med, 217, e20201181.

      7. Shen, F., Yang, C. X., Lu, Y., Zhang, M., Tian, R. R., Dong, X. Q., Li, A. Q., Zheng, Y. T., Pang, W., 2023. Significant neutralizing escapes of Omicron and its sublineages in SARS-CoV-2-infected individuals vaccinated with inactivated vaccines. J Med Virol, 95, e28516.

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

      9. Yue, C., Song, W., Wang, L., Jian, F., Chen, X., Gao, F., Shen, Z., Wang, Y., Wang, X., Cao, Y., 2023. ACE2 binding and antibody evasion in enhanced transmissibility of XBB.1.5. Lancet Infect Dis, 23, 278-280.

      10. Zhang, L., Kempf, A., Nehlmeier, I., Cossmann, A., Dopfer-Jablonka, A., Stankov, M. V., Schulz, S. R., Jäck, H. M., Behrens, G. M. N., Pöhlmann, S., Hoffmann, M., 2023. Neutralisation sensitivity of SARS-CoV-2 lineages EG.5.1 and XBB.2.3. Lancet Infect Dis, 23, e391-e392.

      11. Zhu, A., Wei, P., Man, M., Liu, X., Ji, T., Chen, J., Chen, C., Huo, J., Wang, Y., Zhao, J., 2023. Antigenic characterization of SARS-CoV-2 Omicron subvariants XBB.1.5, BQ.1, BQ.1.1, BF.7 and BA.2.75.2. Signal Transduct Target Ther, 8, 125.

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    • Electronic Supplementary Material

      10.1016j.virs.2023.11.007-ESM.docx
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      SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

        Corresponding author: Yong-Tang Zheng, zhengyt@mail.kiz.ac.cn
        Corresponding author: Wei Pang, pangw@mail.kiz.ac.cn
      • a. Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China;
      • b. University of Chinese Academy of Sciences, Beijing, 100049, China;
      • c. Yunnan Provincial Infectious Disease Hospital, Kunming, 650399, China;
      • d. Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, China
      • Received Date: 02 August 2023
      • Accepted Date: 22 November 2023

      Abstract: Highlights
      1. Inactivated vaccine breakthrough infection with ancestral or Delta variant induced nearly undetectable nAbs against XBB variants.
      2. Inactivated vaccine breakthrough infection with Omicron BA.1 or BA.5 evoked very weak nAbs against XBB variants.
      3. BA.5 infection induced higher nAbs against XBB variants than BA.1 infection.

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