Characterization of Zika virus binding and enhancement potential of a large panel of flavivirus murine monoclonal antibodies

Willis, Elinor; Hensley, Scott E.

doi:10.1016/j.virol.2017.04.031

Cited by 21 publications

(26 citation statements)

References 43 publications

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“…We demonstrate that ZIKV is able to conduct RNA replication, translation and infectious particle production in subsets of myeloid‐like K562—which is in agreement with previous reports—as well as “erythroid‐differentiated” KU812Ep6 EPO cells. Surprisingly and in contrast to the supposedly representative cell culture models, neither primary CD34 + HSPCs nor differentiated erythroid cells supported ZIKV propagation.…”

Section: Discussionsupporting

confidence: 92%

Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

et al. 2020

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BACKGROUND To date, several cases of transfusion‐transmitted ZIKV infections have been confirmed. Multiple studies detected prolonged occurrence of ZIKV viral RNA in whole blood as compared to plasma samples indicating potential ZIKV interaction with hematopoietic cells. Also, infection of cells from the granulocyte/macrophage lineage has been demonstrated. Patients may develop severe thrombocytopenia, microcytic anemia, and a fatal course of disease occurred in a patient with sickle cell anemia suggesting additional interference of ZIKV with erythroid and megakaryocytic cells. Therefore, we analyzed whether ZIKV propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells. METHODS ZIKV RNA replication, protein translation and infectious particle formation in hematopoietic cell lines as well as primary CD34+ HSPCs and ex vivo differentiated erythroid and megakaryocytic cells was monitored using qRT‐PCR, FACS, immunofluorescence analysis and infectivity assays. Distribution of ZIKV RNA and infectious particles in spiked red blood cell (RBC) units or platelet concentrates (PCs) was evaluated. RESULTS While subsets of K562 and KU812Ep6EPO cells supported ZIKV propagation, primary CD34+ HSPCs, MEP cells, RBCs, and platelets were non‐permissive for ZIKV infection. In spiking studies, ZIKV RNA was detectable for 7 days in all fractions of RBC units and PCs, however, ZIKV infectious particles were not associated with erythrocytes or platelets. CONCLUSION Viral particles from plasma or contaminating leukocytes, rather than purified CD34+ HSPCs or the cellular component of RBC units or PCs, present the greatest risk for transfusion‐transmitted ZIKV infections.

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Section: Discussionsupporting

confidence: 92%

Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

et al. 2020

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“…All together these observations strongly suggest that covalently linked E dimer can bring even higher benefits to the development of a DENV vaccine. In vitro tests performed with DENV-positive sera or DENV monoclonal antibodies showed cross-reactivity and ADE of ZIKV infection, similar to experiments performed in mouse models (20,(45)(46)(47). In other cases analysis performed in non-human primate models ruled out a negative effect of previous DENV exposure on ZIKV infection (48), which was later confirmed by population studies with asymptomatic ZIKV infection in subjects positive for DENV antibodies (49).…”

Section: Discussionsupporting

confidence: 66%

Zika virus-like particles bearing covalent dimer of envelope protein protect mice from lethal challenge

Lorenzo

Tandavanitj

Doig

et al. 2020

Preprint

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Zika virus (ZIKV) envelope (E) protein is the major target of neutralizing antibodies in infected host, and thus represents a candidate of interest for vaccine design. However, a major concern in the development of vaccines against ZIKV and the related dengue virus is the induction of cross-reactive poorly neutralizing antibodies that can cause antibody-dependent enhancement (ADE) of infection. This risk necessitates particular care in vaccine design. Specifically, the engineered immunogens should have their cross-reactive epitopes masked, and they should be optimized for eliciting virus-specific strongly neutralizing antibodies upon vaccination. Here, we developed ZIKV subunit- and virus-like particle (VLP)-based vaccines displaying E in its wild type form, or E locked in a covalently linked dimeric (cvD) conformation to enhance the exposure of E dimers to the immune system. Compared with their wild-type derivatives, cvD immunogens elicited antibody with higher capacity of neutralizing virus infection of cultured cells. More importantly, these immunogens protected animals from lethal challenge with both the African and Asian lineages of ZIKV, impairing virus dissemination to brain and sexual organs. Moreover, the locked conformation of E reduced the exposure of epitopes recognized by cross-reactive antibodies and therefore showed a lower potential to induce ADE in vitro. Our data demonstrated a higher efficacy of the VLPs in comparison with the soluble dimer and support VLP-cvD as a promising ZIKV vaccine.

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“…2B) potent neutralizing MAb generated and sold by Integral Molecular that binds a quaternary epitope across Domain II (DII) and Domain III (DIII) of adjacent ZIKV E protein monomers. MAbs 4G2, 1N5, and 4E8 are pan-flavivirus MAbs that neutralize DENV by binding epitopes in the fusion loop (26) but are known not to neutralize ZIKV (40,41). As predicted, ZIKV RVPs were neutralized by 1C19, C8, C10, and LM-081, but not by control MAbs 4G2, 1N5, and 4E8.…”

Section: Zikv Rvps Are Infectious and Antigenically Identical To Livementioning

confidence: 62%

Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications

Whitbeck

Thomas

Kadash-Edmondson

et al. 2020

Preprint

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The development of vaccines against flaviviruses, including Zika virus (ZIKV) and dengue virus (DENV), continues to be a major challenge, hindered by the lack of efficient and reliable methods for screening neutralizing activity of sera or antibodies. To address this need, we previously developed a plasmid-based, replication-incompetent DENV reporter virus particle (RVP) production system as an efficient and safe alternative to the Plaque Reduction Neutralization Test (PRNT). As part of the response to the 2015-2016 ZIKV outbreak, we recently developed pseudoinfectious ZIKV RVPs by modifying our DENV RVP system. The use of ZIKV RVPs as critical reagents in human clinical trials requires their further validation using stability and reproducibility metrics for large-scale applications. In the current study, we validated ZIKV RVPs using infectivity, neutralization, and enhancement assays with monoclonal antibodies (MAbs) and human ZIKV-positive patient serum. ZIKV RVPs are antigenically identical to live virus based on binding ELISA and neutralization results and are nonreplicating based on the results of plaque formation assays. We demonstrate reproducible neutralization titer data (NT50 values) across different RVP production lots, volumes, time frames, and laboratories. We also show RVP stability across experimentally relevant time intervals and temperatures. Our results demonstrate that ZIKV RVPs provide a safe, rapid, and reproducible reagent for large-scale, long-term studies of neutralizing antibodies and sera, which can facilitate large-scale screening and epidemiological studies to help expedite ZIKV vaccine development.

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Characterization of Zika virus binding and enhancement potential of a large panel of flavivirus murine monoclonal antibodies

Cited by 21 publications

References 43 publications

Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

Zika virus-like particles bearing covalent dimer of envelope protein protect mice from lethal challenge

Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications

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Characterization of Zika virus binding and enhancement potential of a large panel of flavivirus murine monoclonal antibodies

Cited by 21 publications

References 43 publications

Zika virus infection studies with CD34+ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

Zika virus infection studies with CD34+ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

Zika virus-like particles bearing covalent dimer of envelope protein protect mice from lethal challenge

Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications

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Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets

Zika virus infection studies with CD34⁺ hematopoietic and megakaryocyte‐erythroid progenitors, red blood cells and platelets