| Literature DB >> 33377126 |
Huy A Tu1,2, Usha K Nivarthi3, Nancy R Graham1, Philip Eisenhauer4, Matthew J Delacruz3, Kristen K Pierce1,4, Stephen S Whitehead5, Jonathan E Boyson2,6, Jason W Botten1,2,4, Beth D Kirkpatrick1,4, Anna P Durbin7, Aravinda M deSilva3, Sean A Diehl1,2.
Abstract
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.Entities:
Keywords: CD4 T cells; TV003; dengue vaccine; humoral immune response; memory B cells; neutralizing antibodies; protective immunity; serotype-specific antibodies; tetravalent live attenuated vaccine
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Year: 2020 PMID： 33377126 PMCID： PMC7762770 DOI： 10.1016/j.xcrm.2020.100155
Source DB: PubMed Journal: Cell Rep Med ISSN： 2666-3791