Abstract：
BACKGROUND: Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of \"future\" variants in the context of such heterogeneous exposure has not been studied.
METHODS: We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework.
RESULTS: Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both \'High S\' and \'Low S\' of Delta and Omicron periods were closely related to \"future\" subvariants by Antigenic Cartography. Sera from different S groups clustered together with \'Low S\' interspersed between \'High S\' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies.
CONCLUSIONS: Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to \"future\" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the \'Low S\' antibody demonstrates similar binding.
METHODS: We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework.
RESULTS: Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both \'High S\' and \'Low S\' of Delta and Omicron periods were closely related to \"future\" subvariants by Antigenic Cartography. Sera from different S groups clustered together with \'Low S\' interspersed between \'High S\' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies.
CONCLUSIONS: Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to \"future\" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the \'Low S\' antibody demonstrates similar binding.
摘要：
背景：在整个COVID-19大流行期间，病毒进化和大规模疫苗接种计划导致了SARSCoV-2刺突蛋白的多次暴露，导致复杂的抗体谱。在这种异质暴露的背景下，尚未研究这些与“未来”变体的刺突蛋白的结合。
方法：我们测试了通过抗刺突抗体（包括IgG）水平分层的存档血清（Delta和Omicron期）对Omicron亚变体（BA.1，BA.2，BA.2.12.1，BA.2.75，BA.4/5和BF.7）刺突蛋白的反应性。使用抗原制图评估组间的抗原距离，并在欧几里得距离框架中对抗体数据进行分层聚类。
结果：抗体（包括IgG）抗体对野生型（CLIA）和亚变体（ELISA）刺突蛋白的反应性在各个时期之间相似（p>0.05）。Delta和Omicron期的\'高S\'和\'低S\'都与抗原制图的“未来”亚变体密切相关。来自不同S组的血清与\'低S\'一起散布在分层聚类上的\'高S\'之间，提示共同的结合位点。Further,野生型(S1/S2和三聚体S)的抗刺突抗体(包括IgG)与Omicron亚变体结合抗体成簇。
结论：由Delta或Omicron时期的累积病毒暴露引起的混合免疫导致与“未来”变体的等效结合，这可能是由于与未来变体的刺突蛋白的保守区域结合。一个突出的发现是\'低S\'抗体表现出相似的结合。
方法：我们测试了通过抗刺突抗体（包括IgG）水平分层的存档血清（Delta和Omicron期）对Omicron亚变体（BA.1，BA.2，BA.2.12.1，BA.2.75，BA.4/5和BF.7）刺突蛋白的反应性。使用抗原制图评估组间的抗原距离，并在欧几里得距离框架中对抗体数据进行分层聚类。
结果：抗体（包括IgG）抗体对野生型（CLIA）和亚变体（ELISA）刺突蛋白的反应性在各个时期之间相似（p>0.05）。Delta和Omicron期的\'高S\'和\'低S\'都与抗原制图的“未来”亚变体密切相关。来自不同S组的血清与\'低S\'一起散布在分层聚类上的\'高S\'之间，提示共同的结合位点。Further,野生型(S1/S2和三聚体S)的抗刺突抗体(包括IgG)与Omicron亚变体结合抗体成簇。
结论：由Delta或Omicron时期的累积病毒暴露引起的混合免疫导致与“未来”变体的等效结合，这可能是由于与未来变体的刺突蛋白的保守区域结合。一个突出的发现是\'低S\'抗体表现出相似的结合。
