Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased T FH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of T FH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.

中文翻译：

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两剂初免免疫通过将疫苗递送与生发中心反应同步来增强体液免疫


在原发性免疫反应期间延长亚单位疫苗暴露时间可增强体液免疫。递增剂量免疫 （EDI） 是每隔一天接种疫苗，在 2 周内逐渐增加，特别有效，但在临床上难以实施。在这里，使用 HIV Env 三聚体/皂苷佐剂疫苗，我们探索了简化的 EDI 方案，发现接种 20% 的疫苗，然后在 7 天后接种剩余的 80% 的剂量的两针方案增加了 T FH 反应 6 倍，抗原特异性生发中心 （GC） B 细胞增加了 10 倍，血清抗体滴度增加了 10 倍与推注免疫相比。T FH 启动和 GC 反应的计算模型表明，树突状细胞上的激活/抗原负载增加和滤泡树突状细胞对第二剂中递送的抗原捕获增加有助于这些效果，我们通过实验验证了预测。这些结果表明，两针启动方法可用于显着增强对亚单位疫苗的反应。