Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

Matthew H Collins,Aravinda M De Silva,Ellen Young,Ramesh Jadi,Cesar A Lopez,Helen M Lazear,Eileen Mcgowan,Ralph S Baric

doi:10.3201/eid2305.161630

Abstract

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus–specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

Highlights

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests
The panel comprised serum from 21 persons exposed to primary flavivirus infections and serum from 15 persons exposed to >2 flavivirus infections, including 2 persons exposed to both DENV and Zika virus
Plasmablasts isolated from patients during or immediately after recovery from acute DENV infection produced antibodies that cross-neutralized Zika virus in cell culture [35] and were protective in a mouse model of Zika virus infection [18]

Summary

Introduction

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Distinct from other flaviviruses, Zika virus infection during pregnancy can result in a spectrum of developmental abnormalities (congenital Zika syndrome) [5], which can include ocular damage, microcephaly, and fetal death [6] These manifestations raise public health challenges unique from those of other vectorborne diseases, preventing sexual transmission and protecting pregnant women. Several groups recently reported that antibodies isolated from persons with prior DENV infections cross-neutralize Zika virus and cross-protect in animal models of Zika virus infection [15,16,17,18,19]. During 2016 in North Carolina, USA, we studied whether persons exposed to DENV maintain cross-neutralizing antibodies to Zika virus

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Conclusion