Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC, USA.
Cell Rep. 2022 Jun 7;39(10):110930. doi: 10.1016/j.celrep.2022.110930.
The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses of humans. Several live-attenuated tetravalent DENV vaccines are at different stages of clinical development and approval. In children with no baseline immunity to DENVs, a leading vaccine (Dengvaxia) is efficacious against vaccine-matched DENV4 genotype II (GII) strains but not vaccine-mismatched DENV4 GI viruses. We use a panel of recombinant DENV4 viruses displaying GI or GII envelope (E) proteins to map Dengvaxia-induced neutralizing antibodies (NAbs) linked to protection. The vaccine stimulated antibodies that neutralize the DENV4 GII virus better than the GI virus. The neutralization differences map to 5 variable amino acids on the E protein located within a region targeted by DENV4 NAbs, supporting a mechanistic role for these epitope-specific NAbs in protection. In children with no baseline immunity to DENVs, levels of DENV4 serotype- and genotype-specific NAbs induced by vaccination are predictive of vaccine efficacy.
登革热病毒有 4 种血清型（DENV1-4），均为可感染人类的黄病毒属蚊媒病毒。几种减毒活的四价登革热病毒疫苗目前处于不同的临床开发和审批阶段。在无登革热基线免疫力的儿童中，一种主要的疫苗（Dengvaxia）对疫苗匹配的 DENV4 基因型 II（GII）株有效，但对疫苗不匹配的 DENV4 GI 病毒无效。我们使用一组展示 GI 或 GII 包膜（E）蛋白的重组 DENV4 病毒，来绘制与保护作用相关的 Dengvaxia 诱导的中和抗体（NAb）。疫苗刺激的抗体对 DENV4 GII 病毒的中和作用优于 GI 病毒。中和差异映射到 E 蛋白上位于 DENV4 NAb 靶向区域内的 5 个可变氨基酸，支持这些表位特异性 NAb 在保护中的作用机制。在无登革热基线免疫力的儿童中，疫苗接种诱导的 DENV4 血清型和基因型特异性 NAb 水平可预测疫苗的疗效。
