Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Tokyo Shinagawa Hospital, Tokyo 140-8522, Japan.
Sci Transl Med. 2024 Aug 21;16(761):eadp9927. doi: 10.1126/scitranslmed.adp9927.
Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines. After a second BA.5 exposure, B cells with BA.5 spike protein-skewed reactivity were promptly elicited, correlating with preexisting antibody titers. Clonal lineage analysis identified BA.5-skewed B cells that had redirected their specificity from the ancestral strain to BA.5 through somatic hypermutations. Moreover, B cells with redirected BA.5 specificity exhibited accelerated development compared with de novo B cells derived from naïve repertoires. This redirected BA.5 specificity demonstrated greater resilience to viral point mutation and adaptation to recent Omicron variants HK.3 and JN.1, months after the second BA.5 exposure, suggesting that existing B cells elicited by older vaccines can redirect their specificity toward newly evolving variants.
人们认为，祖先 SARS-CoV-2 株的免疫印迹会阻碍基于奥密克戎的加强疫苗对奥密克戎特异性体液反应的强烈诱导。在这里，我们分析了先前被基于 mRNA 疫苗的祖先株免疫印迹的个体在反复接触 BA.5 后记忆 B（B）细胞的特异性和中和活性。在第二次接触 BA.5 后，迅速引发了对 BA.5 刺突蛋白呈偏倚反应的 B 细胞，这与预先存在的抗体滴度相关。克隆谱系分析确定了通过体细胞超突变将特异性从祖先株重定向到 BA.5 的 BA.5 偏倚 B 细胞。此外，与源自幼稚库的新生成 B 细胞相比，具有重定向 BA.5 特异性的 B 细胞表现出更快的发育。这种重定向的 BA.5 特异性对病毒点突变具有更强的抵抗力，并能适应最近的奥密克戎变体 HK.3 和 JN.1，这是在第二次接触 BA.5 后数月，这表明由旧疫苗引发的现有 B 细胞可以将其特异性重新定向到新出现的变体。
