Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics

Abstract

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.

Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics

“…It was also demonstrated that distinct dengue-infected individuals develop variable titers of antibodies that recognize a specific neutralizing epitope ( 85 ). Two recent studies identified and characterized the functional activity and B-cell lineage of broadly neutralizing dengue antibodies ( 72 ) and demonstrated that activated, clonally expanded T cells that become committed to the dengue repertoire have a unique transcriptional signature ( 86 ). More specifically, this last study applied single-cell RNA sequencing on T-cell receptor (TCR) immune repertoires.…”

Safety and Considerations of the COVID-19 Vaccine Massive Deployment

“…However, it is too early to reject the hypothesis that vaccination with COVID-19 vaccines barely cause ADE. Researches indicated ADE could happen at sub-neutralizing concentrations of the antibodies when cells were infected by HIV-1, DENV or Enterovirus 71 (EV71) (Chen et al 2013;Durham et al 2019;Meyer et al 2011). With the weaning on immune response induced by current vaccination program of COVID-19 vaccines, there is stubborn potential of ADE caused when immunized people is infected by SARS-CoV-2.…”

Memory B cell and antibody responses to flavivirus infection and vaccination

“…Durham et al . previously used transcriptomic analysis and identified novel recognition determinants of bNAbs within the DENV EDI region 41 .…”