Convergent Antibody Signatures in Human Dengue
Poornima Parameswarana b, Yi Liuc d, Krishna M. Roskinb, Katherine Jacksonb, Vaishali P. Dixitb, Ji-Yeun Leeb, Karen L. Artilesb, Simona Zompìa, Maria José Vargase, Birgitte B. Simenf, Bozena Hanczarukf, Kim McGowanf
- aDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA
- bDepartment of Pathology, Stanford University, Stanford, CA 94305, USA
- cBiomedical Informatics Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA
- dDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA
- eLaboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua 16064, Nicaragua
- f454 Life Sciences, a Roche Company, Branford, CT 06405, USA
- gBaskin School of Engineering, University of California at Santa Cruz, Santa Cruz, CA 95064, USA
- hDepartment of Genetics, Stanford University, Stanford, CA 94305, USA
- ✉Corresponding author
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Abstract
Dengue is the most prevalent mosquito-borne viral disease in humans, and the lack of early prognostics, vaccines, and therapeutics contributes to immense disease burden. To identify patterns that could be used for sequence-based monitoring of the antibody response to dengue, we examined antibody heavy-chain gene rearrangements in longitudinal peripheral blood samples from 60 dengue patients. Comparing signatures between acute dengue, postrecovery, and healthy samples, we found increased expansion of B cell clones in acute dengue patients, with higher overall clonality in secondary infection. Additionally, we observed consistent antibody sequence features in acute dengue in the highly variable major antigen-binding determinant, complementarity-determining region 3 (CDR3), with specific CDR3 sequences highly enriched in acute samples compared to postrecovery, healthy, or non-dengue samples. Dengue thus provides a striking example of a human viral infection where convergent immune signatures can be identified in multiple individuals. Such signatures could facilitate surveillance of immunological memory in communities.