@article{f8a33c3f33d64c21b5beb05187d6be7f,
title = "Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model",
abstract = "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: We utilized 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 of MBC and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotype-specific response in both compartments. The serum response 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. Funding: This study was supported by the Bill and Melinda Gates Foundation and the National Institutes of Health.",
keywords = "Antibody, Dengue, Humoral immunity, Viral infection",
author = "Nivarthi, {Usha K.} and Tu, {Huy A.} and Delacruz, {Matthew J.} and Jesica Swanstrom and Bhumi Patel and Durbin, {Anna P.} and Whitehead, {Stephen S.} and Pierce, {Kristen K.} and Kirkpatrick, {Beth D.} and Baric, {Ralph S.} and Ngan Nguyen and Emerling, {Daniel E.} and {de Silva}, {Aravinda M.} and Diehl, {Sean A.}",
note = "Funding Information: We thank the study volunteers and clinical staff at the University of Vermont Vaccine Testing Center and the Johns Hopkins Center for Immunization Research. At the University of Vermont, cell sorting and flow cytometric analysis was performed at the Bassett Flow Cytometry and Cell Sorting Facility (with thanks to Roxana del Rio-Guerra, PhD) and supported by National Institutes of Health grants S10-ODO18175 and P30GM118228. We thank Patrick Wilson (U. Chicago) for IgG1, Ig-κ, and Ig-λ expression plasmids (see ref. [ 52 ] and Benjamin McElvany (U. Vermont) for generation of mAbs from MBCs. Funding Information: This study was supported by the Bill and Melinda Gates Foundation (OPP110470), the National Institutes of Allergy and Infectious Disease (R01 AI107731?05 to A.DS, and T32AI055402 to H.T.), and the National Institutes of General Medical Sciences (P20GM125498 to B.D.K. and S.A.D.). The clinical trials from which samples were obtained were funded by NIAID Intramural contract HHSN272200900010C. The funders had no role in the study design; in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. We thank the study volunteers and clinical staff at the University of Vermont Vaccine Testing Center and the Johns Hopkins Center for Immunization Research. At the University of Vermont, cell sorting and flow cytometric analysis was performed at the Bassett Flow Cytometry and Cell Sorting Facility (with thanks to Roxana del Rio-Guerra, PhD) and supported by National Institutes of Health grants S10-ODO18175 and P30GM118228. We thank Patrick Wilson (U. Chicago) for IgG1, Ig-? and Ig-? expression plasmids (see ref. [52] and Benjamin McElvany (U. Vermont) for generation of mAbs from MBCs. Funding Information: This study was supported by the Bill and Melinda Gates Foundation ( OPP110470 ), the National Institutes of Allergy and Infectious Disease ( R01 AI107731–05 to A.DS, and T32AI055402 to H.T.), and the National Institutes of General Medical Sciences ( P20GM125498 to B.D.K. and S.A.D.). The clinical trials from which samples were obtained were funded by NIAID Intramural contract HHSN272200900010C . The funders had no role in the study design; in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = mar,
doi = "10.1016/j.ebiom.2019.02.060",
language = "English (US)",
volume = "41",
pages = "465--478",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}