Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

SARS-CoV-2重组毒株的出现尤其值得关注，因其可通过抗原转变（antigenic shift）引发免疫逃逸能力的突发提升。近期出现的重组毒株XBB及XBB.1.5，相较于此前的德尔塔克戎（Deltacron）等重组毒株，具有更高的传播能力。我们提出假说：针对SARS-CoV-2重组毒株的免疫水平，取决于个体此前接触其亲本毒株的经历。为验证这一假说，我们检测了通过感染、疫苗接种或突破性感染所获得的德尔塔（Delta）或奥密克戎（BA.1或BA.2）免疫，能否中和德尔塔克戎（Deltacron）以及XBB/XBB.1.5重组毒株。研究发现，相较于疫苗加强针接种，德尔塔、BA.1或BA.2突破性感染所提供的免疫保护，对德尔塔克戎及其亲本毒株的防护效果更佳。除BA.2突破性感染组的血清外，所有血清样本均无法有效中和XBB谱系毒株及其亲本BA.2.75.2。上述结果验证了我们提出的假说。本研究结果进一步凸显了匹配当前流行关切毒株抗原特征的多价疫苗的重要性，同时也表明针对特定变异株的诊断工具可指导公共卫生决策与个体应对新发SARS-CoV-2重组毒株的相关选择。