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Cell Host Microbe:张文宏等团队研究灭活疫苗对Omicron变种的中和作用

2022-05-10 网络 网络

当前,SARS-CoV-2 奥密克戎 (Omicron) 变异株已在全世界大范围流行,世卫组织从一开始就将其列为受关注的变异株 (VOC) 。该变异株被划分为四

当前,SARS-CoV-2 奥密克戎 (Omicron) 变异株已在全世界大范围流行,世卫组织从一开始就将其列为受关注的变异株 (VOC) 。该变异株被划分为四个子谱系,分别命名为:BA.1,BA.1.1,BA.2和BA.3。最初的Omicron (BA.1亚谱系) 于2021年11月在博茨瓦纳和南非首次被发现,并与其衍生变异株BA.1.1 (含有额外的S蛋白R346K突变) 一起在几周内成为全球替代德尔塔 (Delta) 的主导流行株。但随后,研究者看到BA.2的比例迅速飙升,这个亚谱系迅速成为全球的主要变体。因此,迫切需要并排比较所有主要Omicron亚系对现有疫苗引发或单克隆抗体 (mAb) 介导的中和的敏感性。

研究结果发表在最新的一期复旦大学在Cell Host Microbe上,题目为: Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages 的论文,由复旦大学附属华山医院张文宏团队和复旦大学生命科学学院王鹏飞团队合作。这项研究结果此前发表在预印本上,梅斯也进行了相关报道:bioRxiv:张文宏新作:全面评价奥密克戎逃逸能力!

研究者之前就报道过对恢复期或BBIBP-CorV疫苗接种血清的BA.1的中和活性显着降低。在这里,研究者显示所有多克隆血清在与其他Omicron亚系的中和活性方面也显着损失,其下降幅度与BA.1相当甚至更大,表明所有这些亚谱系与WT病毒具有非常远的抗原距离。研究者的结果与mRNA疫苗的研究非常相似,显示针对BA.2的中和抗体滴度与BA.1相似或低于BA.1。基于这些,研究者认为BA.2相对于BA.1的选择性优势应该主要归因于其更高的传播性而不是免疫逃避。
另一方面,研究者表明接种同源灭活疫苗加强剂或异源蛋白质亚单位疫苗加强剂可以显着提高BA.1的中和滴度。对于其他Omicron亚系也是如此。最近,已经报道了三种重组谱系 (XD,XE和XF) ,但它们的抗体逃避应该与这里研究的Omicron亚系没有显着差异,因为它们的S蛋白与BA.1或BA.2相同。因此,推广疫苗加强针注射仍然是预防SARS-CoV-2传播的有效手段。

接种2-3剂BBIBP-CorV灭活病毒疫苗,或者第3剂接种智飞疫苗ZF001对Omicron的4种亚型BA.1,BA.1.1,BA.2,BA.3的中和活性。研究应用VSV假病毒系统评估了上述疫苗接种者血清对于4种亚型的中和活性。研究发现,2剂BBIBP-CorV接种者血清对原始野生型中和滴度ID50为55,但对4种Omicron突变株都没有中和活性。

3剂BBIBP-CorV对BA.1中和滴度ID50为<63,对BA.1.1为<48,对BA.2为<56,对BA.3为<57。2剂BBIBP-CorV+1剂ZF001对BA.1中和滴度ID50为108,对BA.1.1为81,对BA.2为<42,对BA.3为69。目前以BA.2为主,即使是三针国药灭活疫苗,或两针国药灭活疫苗加上一针重组蛋白疫苗异源接种,对BA.2的中和作用仍然不理想。

研究还用单克隆抗体 (mAbs) 研究了Omicron亚系的免疫逃逸能力。与研究者对BA.1的报告类似,大多数mAbs对BA.1.1、BA.2和BA.3的中和活性完全或大幅度丧失。但研究者确实观察到这些亚系中的某些mAbs有一些不同的中和模式,反映了它们不同的变异。例如,S309和5-7,针对RBD或NTD中的一些独特的位点,是两个据报道对BA.1基本保持活性的mAbs,但它们的活性被BA.2进一步逃逸。

相反,一些mAbs如COV2-2130和2-7对BA.1完全失去了活性,但对BA.2又恢复了活性。好消息是LY-CoV1404(bebtelovimab)对所有Omicron亚系和其他主要的SARS-CoV-2变体都保持有效的中和活性。该研究的数据与其他关于Omicron亚系和单一突变的mAb中和情况有很好的一致性。研究还添加了对BA.3的免疫逃逸能力研究,并将一些近距离突变结合起来,研究它们的协同作用。

如上图,尽管LY-CoV1404目前仍然是我们对SARS-CoV-2治疗性抗体的希望,但鉴于RNA病毒的易突变特性,如果将其作为单一疗法长期施用,则可能会出现耐药性。因此,研究者也建议开发更有效和广泛的中和抗体作为混合治疗使用,以对抗这种不断变异的病原体。同时,疫苗加强针,无论是同源的还是异源的,都可以引发中和抗体,有助于减少病毒逃逸,应该持续推广加强针接种,并研发新型高效疫苗。

这项研究结果与此前多项研究结果的结论是相似的,如:

Emerg Microbes Infect:张文宏团队发现异源序贯加强免疫接种,对奥密克戎效果更好

Nature五连发:评估奥密克戎突变株对疫苗和抗体的逃逸

奥密克戎(Omicron)对疫苗的影响:辉瑞疫苗中和能力下降41倍

中和抗体能对抗奥密克戎(Omicron)突变株吗?谢晓亮教授给您答案(附下载)

原始出处:

Ai, J., Wang, X., He, X., Zhao, X., Zhang, Y., Jiang, Y., Li, M., Cui, Y., Chen, Y., Qiao, R., Li, L., Yang, L., Li, Y., Hu, Z., Zhang, W., Wang, P., Antibody Evasion of SARSCoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages, Cell Host and Microbe (2022), doi: https:// doi.org/10.1016/j.chom.2022.05.001.

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    2022-11-08 xjy02
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