1. Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model
- Author
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Jesica Swanstrom, Daniel Emerling, Kristen K. Pierce, Usha K. Nivarthi, Sean A. Diehl, Beth D. Kirkpatrick, Aravinda M. de Silva, Stephen S. Whitehead, Anna P. Durbin, Huy A. Tu, Ralph S. Baric, Ngan Nguyen, Bhumi Patel, and Matthew J. Delacruz
- Subjects
0301 basic medicine ,biology ,medicine.drug_class ,General Medicine ,Dengue virus ,medicine.disease ,Monoclonal antibody ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,3. Good health ,Dengue fever ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Viral envelope ,030220 oncology & carcinogenesis ,Humoral immunity ,Immunology ,biology.protein ,medicine ,Antibody ,B cell - 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.
- Published
- 2019