Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4⁺ T cell and memory B cell responses. Antigen-specific CD4⁺ T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.

中文翻译：

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AS03 佐剂可增强人类记忆 B 细胞对植物性 COVID-19 疫苗的反应程度、持久性和克隆广度

疫苗佐剂增加了血清抗体反应的广度，但这是否是由于具有不同特异性的抗原特异性 B 细胞克隆的产生，或者是由于产生广泛交叉反应抗体的记忆 B 细胞克隆的成熟所致，尚不清楚。在这里，我们纵向分析了健康成年人在接种两剂疫苗后的免疫反应，其中包括病毒样颗粒 COVID-19 疫苗 (CoVLP)、辅以 AS03 的 CoVLP (CoVLP+AS03) 或信使 RNA 疫苗 (mRNA-1273) 。 CoVLP+AS03增强了循环抗体以及抗原特异性CD4 ⁺ T细胞和记忆B细胞反应的强度和持久性。 CoVLP+AS03 组中第 42 天的抗原特异性 CD4 ⁺ T 细胞与第 6 个月时的抗原特异性记忆 B 细胞相关。 CoVLP+AS03 诱导记忆 B 细胞反应，在 6 个月内积累体细胞超突变，导致单克隆抗体的中和广度增强。此外，记忆 B 细胞编码的广泛中和抗体的比例在第 42 天至第 6 个月期间有所增加。这些结果表明，AS03 在克隆水平上增强了 B 细胞记忆的抗原广度，并诱导 B 细胞反应逐渐成熟。