Dataset Information

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

ABSTRACT: Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

SUBMITTER: Robbiani DF

PROVIDER: S-EPMC5492969 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Robbiani Davide F DF Bozzacco Leonia L Keeffe Jennifer R JR Khouri Ricardo R Olsen Priscilla C PC Gazumyan Anna A Schaefer-Babajew Dennis D Avila-Rios Santiago S Nogueira Lilian L Patel Roshni R Azzopardi Stephanie A SA Uhl Lion F K LFK Saeed Mohsan M Sevilla-Reyes Edgar E EE Agudelo Marianna M Yao Kai-Hui KH Golijanin Jovana J Gristick Harry B HB Lee Yu E YE Hurley Arlene A Caskey Marina M Pai Joy J Oliveira Thiago T Wunder Elsio A EA Sacramento Gielson G Nery Nivison N Orge Cibele C Costa Federico F Reis Mitermayer G MG Thomas Neena M NM Eisenreich Thomas T Weinberger Daniel M DM de Almeida Antonio R P ARP West Anthony P AP Rice Charles M CM Bjorkman Pamela J PJ Reyes-Teran Gustavo G Ko Albert I AI MacDonald Margaret R MR Nussenzweig Michel C MC

Cell 20170501 4

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expa ...[more]

PMID: 28475892

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Project description:Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIII-targeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines.IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIII-specific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines.

Dataset Information

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Publications

Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

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