Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

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.

Keywords: CD4 T cells; TV003; dengue vaccine; humoral immune response; memory B cells; neutralizing antibodies; protective immunity; serotype-specific antibodies; tetravalent live attenuated vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology*
  • Dengue / immunology
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology
  • Flavivirus / immunology*
  • Humans
  • Plasma Cells / immunology
  • Vaccines, Attenuated / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated