Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Sci Immunol. 2024 Sep 20;9(99):eadl3755. doi: 10.1126/sciimmunol.adl3755.
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 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 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.
在初次免疫反应期间延长亚单位疫苗的暴露时间可增强体液免疫。递增剂量免疫（EDI），即在 2 周内每隔一天以递增的方式给予疫苗，特别有效，但在临床上实施具有挑战性。在这里，我们使用 HIV Env 三聚体/皂苷佐剂疫苗探索了简化的 EDI 方案，发现两剂方案，先给予 20%的疫苗，然后在 7 天后给予剩余的 80%剂量，可使 T 反应增加 6 倍，抗原特异性生发中心（GC）B 细胞增加 10 倍，血清抗体滴度增加 10 倍，与单次免疫相比。T 细胞启动和 GC 反应的计算模型表明，增强树突状细胞的激活/抗原加载以及第二次剂量中滤泡树突状细胞摄取增加的抗原有助于产生这些效应，我们通过实验验证了这些预测。这些结果表明，两剂免疫接种方案可用于大大增强亚单位疫苗的反应。
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