Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications.
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...
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ftdoajarticles:oai:doaj.org/article:c7e7952329a2425385d3c09278e4276d 2023-05-15T15:09:15+02:00 Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. J Charles Whitbeck Anu Thomas Kathryn Kadash-Edmondson Ariadna Grinyo-Escuer Lewis J Stafford Celine Cheng Grant C Liao Frederick W Holtsberg M Javad Aman Graham Simmons Edgar Davidson Benjamin J Doranz 2020-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008730 https://doaj.org/article/c7e7952329a2425385d3c09278e4276d EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008730 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008730 https://doaj.org/article/c7e7952329a2425385d3c09278e4276d PLoS Neglected Tropical Diseases, Vol 14, Iss 11, p e0008730 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008730 2022-12-31T05:55:01Z 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 developed pseudo-infectious 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 equivalent to live virus based on binding ELISA and neutralization results and are nonreplicating based on the results of live virus replication 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, high-throughput, 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 11 e0008730 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 J Charles Whitbeck Anu Thomas Kathryn Kadash-Edmondson Ariadna Grinyo-Escuer Lewis J Stafford Celine Cheng Grant C Liao Frederick W Holtsberg M Javad Aman Graham Simmons Edgar Davidson Benjamin J Doranz Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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 developed pseudo-infectious 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 equivalent to live virus based on binding ELISA and neutralization results and are nonreplicating based on the results of live virus replication 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, high-throughput, 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. |
format |
Article in Journal/Newspaper |
author |
J Charles Whitbeck Anu Thomas Kathryn Kadash-Edmondson Ariadna Grinyo-Escuer Lewis J Stafford Celine Cheng Grant C Liao Frederick W Holtsberg M Javad Aman Graham Simmons Edgar Davidson Benjamin J Doranz |
author_facet |
J Charles Whitbeck Anu Thomas Kathryn Kadash-Edmondson Ariadna Grinyo-Escuer Lewis J Stafford Celine Cheng Grant C Liao Frederick W Holtsberg M Javad Aman Graham Simmons Edgar Davidson Benjamin J Doranz |
author_sort |
J Charles Whitbeck |
title |
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
title_short |
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
title_full |
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
title_fullStr |
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
title_full_unstemmed |
Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications. |
title_sort |
antigenicity, stability, and reproducibility of zika reporter virus particles for long-term applications. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008730 https://doaj.org/article/c7e7952329a2425385d3c09278e4276d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 11, p e0008730 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008730 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008730 https://doaj.org/article/c7e7952329a2425385d3c09278e4276d |
op_doi |
https://doi.org/10.1371/journal.pntd.0008730 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
11 |
container_start_page |
e0008730 |
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1766340479588237312 |