Background: Acute viral infections induce a rapid and transient increase in antibody-secreting plasmablasts. At
convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible for long-term humoral
immunity. Following an acute viral infection, the specific properties and relationships between antibodies
produced by these B cell compartments are poorly understood.
Methods:Weutilized a controlled human challenge model of primary dengue virus serotype 2 (DENV2) infection
to study acute and convalescent B-cell responses.
Findings: The level of DENV2 replication was correlated with the magnitude of the plasmablast response. Functional
analysis of plasmablast-derived monoclonal antibodies showed that the DENV2-specific response was
dominated by cells producing DENV2 serotype-specific antibodies. DENV2-neutralizing antibodies targeted quaternary
structure epitopes centered on domain III of the viral envelope protein (EDIII). Functional analysis ofMBC
and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotypespecific
response in both compartments. The serumresponse mainly targeted DENV2 serotype-specific epitopes
on EDIII.
Interpretation: Our data suggest overall functional alignment of DENV2-specific responses from the plasmablast,
through the MBC and LLPC compartments following primary DENV2 inflection. These results provide enhanced
resolution of the temporal and specificity of the B cell compartment in viral infection and serve as framework for
evaluation of B cell responses in challenge models
