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 adul...
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ftdoajarticles:oai:doaj.org/article:14dc0a3577d94de2ae361affa396a722 2023-05-15T15:15:20+02:00 Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus. Lo Vang Christopher S Morello Jason Mendy Danielle Thompson Darly Manayani Ben Guenther Justin Julander Daniel Sanford Amit Jain Amish Patel Paul Shabram Jonathan Smith Jeff Alexander 2021-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009195 https://doaj.org/article/14dc0a3577d94de2ae361affa396a722 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009195 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009195 https://doaj.org/article/14dc0a3577d94de2ae361affa396a722 PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009195 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009195 2022-12-31T09:21:59Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Barré ENVELOPE(-68.550,-68.550,-67.500,-67.500) PLOS Neglected Tropical Diseases 15 3 e0009195 |
institution |
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 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Lo Vang Christopher S Morello Jason Mendy Danielle Thompson Darly Manayani Ben Guenther Justin Julander Daniel Sanford Amit Jain Amish Patel Paul Shabram Jonathan Smith Jeff Alexander Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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. |
format |
Article in Journal/Newspaper |
author |
Lo Vang Christopher S Morello Jason Mendy Danielle Thompson Darly Manayani Ben Guenther Justin Julander Daniel Sanford Amit Jain Amish Patel Paul Shabram Jonathan Smith Jeff Alexander |
author_facet |
Lo Vang Christopher S Morello Jason Mendy Danielle Thompson Darly Manayani Ben Guenther Justin Julander Daniel Sanford Amit Jain Amish Patel Paul Shabram Jonathan Smith Jeff Alexander |
author_sort |
Lo Vang |
title |
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_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_sort |
zika virus-like particle vaccine protects ag129 mice and rhesus macaques against zika virus. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009195 https://doaj.org/article/14dc0a3577d94de2ae361affa396a722 |
long_lat |
ENVELOPE(-68.550,-68.550,-67.500,-67.500) |
geographic |
Arctic Barré |
geographic_facet |
Arctic Barré |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009195 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009195 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009195 https://doaj.org/article/14dc0a3577d94de2ae361affa396a722 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009195 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
3 |
container_start_page |
e0009195 |
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1766345695845941248 |