Wang Zuowei, Li Ling, Du Ruiping, Chen Xixian, Sun Yi, Qin Rongrong, Li Yunjian, Feng Hualong, Hu Lin, Chen Xuanyi, Lu Maosheng, Jiang Liwei, Zuo Teng
Laboratory of Immunoengineering, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
iScience. 2024 Dec 9;28(1):111557. doi: 10.1016/j.isci.2024.111557. eCollection 2025 Jan 17.
Whether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines. However, once robustly induced, immune imprinting is not countered by successive Omicron challenges. We compared binding specificities, neutralizing capacities, developing origins and targeting epitopes of monoclonal antibodies from those individuals. Although receptor-binding domain (RBD) and N-terminal domain (NTD) of spike are both primary targets for neutralizing antibodies, immune imprinting only shapes antibody responses to RBD by impeding the production of Omicron-specific neutralizing antibodies while facilitating the development of broadly neutralizing antibodies. We propose that immune imprinting can be either neglected by NTD-based vaccines to induce variant-specific antibodies or leveraged by RBD-containing vaccines to induce broadly neutralizing antibodies.
奥密克戎毒株感染是否能够克服原始新冠病毒的免疫印记仍存在争议。在此，我们分析了接种疫苗和未接种疫苗个体中，由奥密克戎毒株的连续感染所引发的B细胞反应。针对原始新冠病毒及其变体的血浆中和抗体滴度表明，免疫印记并非由灭活疫苗或重组蛋白疫苗持续诱导产生。然而，一旦被强烈诱导，连续的奥密克戎毒株挑战并不能对抗免疫印记。我们比较了这些个体单克隆抗体的结合特异性、中和能力、产生来源和靶向表位。尽管刺突蛋白的受体结合域（RBD）和N端结构域（NTD）都是中和抗体的主要靶点，但免疫印记仅通过阻碍奥密克戎特异性中和抗体的产生，同时促进广泛中和抗体的形成，从而塑造针对RBD的抗体反应。我们提出，基于NTD的疫苗可以忽略免疫印记以诱导变体特异性抗体，而含RBD的疫苗则可以利用免疫印记来诱导广泛中和抗体。
