Primary and secondary dengue virus infections elicit similar memory B cell responses but breadth to other serotypes and cross-reactivity to Zika virus is higher in secondary dengue.

BACKGROUND: The four antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each other and with the closely related Zika flavivirus (ZIKV). The development of polyclonal memory B cells (MBCs) to the four DENV serotypes and ZIKV during DENV infection is not fully understood.

METHODS: Here we analyzed polyclonal MBCs at the single-cell level from peripheral blood mononuclear cells collected ~2 weeks or 6-7 months post-primary or post-secondary DENV infection from a pediatric hospital-based study in Nicaragua using a Multi-Color FluoroSpot assay.

RESULTS: DENV elicits robust type-specific and cross-reactive MBC responses after primary and secondary DENV infection, with a significantly higher cross-reactive response in both. Reactivity to the infecting serotype dominated the total MBC response. While the frequency and proportion of type-specific and cross-reactive MBCs were comparable between primary and secondary DENV infections, within the cross-reactive response, the breadth of MBC responses against different serotypes was greater after secondary DENV infection. DENV infection also induced cross-reactive MBC responses recognizing ZIKV, particularly after secondary DENV infection.

CONCLUSIONS: Overall, our study sheds light on the polyclonal MBC response to DENV and ZIKV in naïve and DENV-pre-immune subjects, with important implications for natural infections and vaccine development.