Establishment of germline-encoded antibodies during primary dengue infection

Dengue viruses impose a major global health burden, while imperfect vaccines raise concerns that the immunization of dengue-naïve individuals may exacerbate disease through immunopathologic mechanisms. Using a controlled human challenge model of primary DENV1 infection, we longitudinally profile B cell receptor repertoires in 9 flavivirus-naïve participants. Despite serological features of primary infection, acute responses are dominated by memory-derived clones in 4/9 participants. We also identify public convergent clones from naive B cells that share sequence features across 7 participants and are enriched for tyrosine-rich CDRH3 motifs. 28 days post infection, these class-switched IgG clones remain relatively germline-like in all participants carrying these public lineages, consistent with early class-switched output before germinal center maturation or a GC-independent pathway. These findings refine models of early antibody responses in dengue and identify germline-like public BCR lineages, including motifs linked to DENV-binding non-neutralizing antibodies, whose specificity and functional role warrant further study.