Department of Microbiology and Molecular Genetics, Vaccine Testing Center, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA.
Cell Rep Med. 2020 Dec 22;1(9):100155. doi: 10.1016/j.xcrm.2020.100155.
The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1-DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understand how vaccine viremia links adaptive immunity and development of protective antibody responses. TV003 viremia triggers an acute plasmablast response that, in combination with DENV-specific CD4 T cells, correlates with serum neutralizing antibodies. TV003 vaccinees develop DENV2-reactive memory B cells, including serotype-specific and multivalent specificities in line with the composition of serum antibodies. There is no post-challenge plasmablast response in vaccinees, although stronger and earlier post-TV003 plasmablast responses associate with sterile humoral protection from DENV2 challenge. TV003 vaccine triggers plasmablasts and memory B cells, which, with support from CD4 T cells, functionally link early vaccine viremia and the serum antibody responses.
四价减毒活登革热候选疫苗 TV003 可诱导针对所有四种登革热病毒血清型（DENV1-DENV4）的中和抗体，并可预防人类 DENV2 实验性攻击。在这里，我们跟踪疫苗病毒血症和 B 和 T 细胞对这种接种/挑战模型的反应，以了解疫苗病毒血症如何将适应性免疫与保护性抗体反应的发展联系起来。TV003 病毒血症引发急性浆母细胞反应，与 DENV 特异性 CD4 T 细胞一起，与血清中和抗体相关。TV003 疫苗接种者产生 DENV2 反应性记忆 B 细胞，包括与血清抗体组成一致的血清型特异性和多价特异性。在疫苗接种者中没有挑战后的浆母细胞反应，尽管更强和更早的 TV003 后浆母细胞反应与 DENV2 挑战的无菌体液保护相关。TV003 疫苗引发浆母细胞和记忆 B 细胞，这些细胞在 CD4 T 细胞的支持下，在功能上连接早期疫苗病毒血症和血清抗体反应。
