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Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient

Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, GA 30033, USA
Author to whom correspondence should be addressed.
These authors contribute equally to this work.
Viruses 2019, 11(1), 19;
Received: 28 November 2018 / Revised: 21 December 2018 / Accepted: 25 December 2018 / Published: 29 December 2018
(This article belongs to the Special Issue Emerging Viruses)
The re-emergence of Zika virus (ZIKV) in the western hemisphere has most significantly affected dengue virus (DENV) endemic regions. Due to the geographical overlap between these two closely related flaviviruses, numerous individuals who suffered ZIKV infection during recent outbreaks may have also previously been exposed to DENV. As such, the impact of pre-existing dengue immunity on immune responses to ZIKV has been an area of focused research and interest. To understand how B cell responses to a ZIKV infection may be modulated by prior dengue exposures, we compared and contrasted plasmablast repertoire and specificity between two ZIKV-infected individuals, one dengue-naïve (ZK018) and the other dengue-experienced (ZK016). In addition to examining serological responses, we generated 59 patient plasmablast-derived monoclonal antibodies (mAbs) to define the heterogeneity of the early B cell response to ZIKV. Both donors experienced robust ZIKV-induced plasmablast expansions early after infection, with comparable mutational frequencies in their antibody variable genes. However, notable differences were observed in plasmablast clonality and functional reactivity. Plasmablasts from the dengue-experienced donor ZK016 included cells with shared clonal origin, while ZK018 mAbs were entirely clonally unrelated. Both at the mAb and plasma level, ZK016 antibodies displayed extensive cross-reactivity to DENV1-4, and preferentially neutralized DENV compared to ZIKV. In contrast, the neutralization activity of ZK018 mAbs was primarily directed towards ZIKV, and fewer mAbs from this donor were cross-reactive, with the cross-reactive phenotype largely limited to fusion loop-specific mAbs. ZK016 antibodies caused greater enhancement of DENV2 infection of FcRγ-expressing cells overall compared to ZK018, with a striking difference at the plasma level. Taken together, these data strongly suggest that the breadth and protective capacity of the initial antibody responses after ZIKV infection may depend on the dengue immune status of the individual. These findings have implications for vaccine design, given the likelihood that future epidemics will involve both dengue-experienced and naïve populations. View Full-Text
Keywords: ZIKV; DENV; antibodies; plasmablast; B-cell; cross-reactivity ZIKV; DENV; antibodies; plasmablast; B-cell; cross-reactivity
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MDPI and ACS Style

Bhaumik, S.K.; Priyamvada, L.; Kauffman, R.C.; Lai, L.; Natrajan, M.S.; Cho, A.; Rouphael, N.; Suthar, M.S.; Mulligan, M.J.; Wrammert, J. Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient. Viruses 2019, 11, 19.

AMA Style

Bhaumik SK, Priyamvada L, Kauffman RC, Lai L, Natrajan MS, Cho A, Rouphael N, Suthar MS, Mulligan MJ, Wrammert J. Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient. Viruses. 2019; 11(1):19.

Chicago/Turabian Style

Bhaumik, Siddhartha K., Lalita Priyamvada, Robert C. Kauffman, Lilin Lai, Muktha S. Natrajan, Alice Cho, Nadine Rouphael, Mehul S. Suthar, Mark J. Mulligan, and Jens Wrammert. 2019. "Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient" Viruses 11, no. 1: 19.

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