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Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus

BACKGROUND: Zika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adu...

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Autores principales: Vang, Lo, Morello, Christopher S., Mendy, Jason, Thompson, Danielle, Manayani, Darly, Guenther, Ben, Julander, Justin, Sanford, Daniel, Jain, Amit, Patel, Amish, Shabram, Paul, Smith, Jonathan, Alexander, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990201/
https://www.ncbi.nlm.nih.gov/pubmed/33711018
http://dx.doi.org/10.1371/journal.pntd.0009195
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author Vang, Lo
Morello, Christopher S.
Mendy, Jason
Thompson, Danielle
Manayani, Darly
Guenther, Ben
Julander, Justin
Sanford, Daniel
Jain, Amit
Patel, Amish
Shabram, Paul
Smith, Jonathan
Alexander, Jeff
author_facet Vang, Lo
Morello, Christopher S.
Mendy, Jason
Thompson, Danielle
Manayani, Darly
Guenther, Ben
Julander, Justin
Sanford, Daniel
Jain, Amit
Patel, Amish
Shabram, Paul
Smith, Jonathan
Alexander, Jeff
author_sort Vang, Lo
collection PubMed
description BACKGROUND: Zika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV. METHODOLOGY/PRINCIPLE FINDINGS: We have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge. CONCLUSIONS/SIGNIFICANCE: These studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials.
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spelling pubmed-79902012021-04-05 Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus Vang, Lo Morello, Christopher S. Mendy, Jason Thompson, Danielle Manayani, Darly Guenther, Ben Julander, Justin Sanford, Daniel Jain, Amit Patel, Amish Shabram, Paul Smith, Jonathan Alexander, Jeff PLoS Negl Trop Dis Research Article BACKGROUND: Zika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV. METHODOLOGY/PRINCIPLE FINDINGS: We have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge. CONCLUSIONS/SIGNIFICANCE: These studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials. Public Library of Science 2021-03-12 /pmc/articles/PMC7990201/ /pubmed/33711018 http://dx.doi.org/10.1371/journal.pntd.0009195 Text en © 2021 Vang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vang, Lo
Morello, Christopher S.
Mendy, Jason
Thompson, Danielle
Manayani, Darly
Guenther, Ben
Julander, Justin
Sanford, Daniel
Jain, Amit
Patel, Amish
Shabram, Paul
Smith, Jonathan
Alexander, Jeff
Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title_full Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title_fullStr Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title_full_unstemmed Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title_short Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus
title_sort zika virus-like particle vaccine protects ag129 mice and rhesus macaques against zika virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990201/
https://www.ncbi.nlm.nih.gov/pubmed/33711018
http://dx.doi.org/10.1371/journal.pntd.0009195
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