Enhancing the germinal center (GC) reaction is a prime objective in vaccine development. Targeting of antigen to MHCII on APCs has previously been shown to increase antibody responses, but the underlying mechanism has been unclear. We have here investigated the GC reaction after targeting antigen to MHCII in (i) a defined model with T and B cells of known specificity using adjuvant-free vaccine proteins, and (ii) an infectious disease model using a DNA vaccine. MHCII-targeting enhanced presentation of peptide: MHCII on APCs, and increased the numbers of GC B cells, T_FH, and plasma cells. Antibodies appeared earlier and levels were increased. BCR of GC B cells and serum antibodies had increased avidity for antigen. The improved responses required cross-linking of BCR and MHCII in either cis or trans. The enhanced GC reaction induced by MHCII-targeting of antigen has clear implications for design of more efficient subunit vaccines.

增强生发中心（GC）反应是疫苗开发的首要目标。先前已证明将抗原靶向 APC 上的 MHCII 可以增加抗体反应，但其潜在机制尚不清楚。我们在这里研究了将抗原靶向 MHCII 后的 GC 反应，其中（i）使用无佐剂疫苗蛋白的已知特异性 T 和 B 细胞的定义模型，以及（ii）使用 DNA 疫苗的传染病模型。_{MHCII 靶向增强肽：MHCII 在 APC 上的呈递，并增加 GC B 细胞、T FH}和浆细胞的数量。抗体出现得更早，水平也更高。GC B 细胞的 BCR 和血清抗体对抗原的亲和力增加。改善的反应需要 BCR 和 MHCII 以顺式或反式交联。MHCII 靶向抗原诱导的增强 GC 反应对于设计更有效的亚单位疫苗具有明显的意义。