A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection
Background Highly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl, causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 cl...
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fthighwire:oai:open-archive.highwire.org:jinfdis:jis232v1 2023-05-15T18:44:12+02:00 A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection Giles, Brendan M. Crevar, Corey J. Carter, Donald M. Bissel, Stephanie J. Schultz-Cherry, Stacey Wiley, Clayton A. Ross, Ted M. 2012-03-23 13:01:32.0 text/html http://jid.oxfordjournals.org/cgi/content/short/jis232v1 https://doi.org/10.1093/infdis/jis232 en eng Oxford University Press http://jid.oxfordjournals.org/cgi/content/short/jis232v1 http://dx.doi.org/10.1093/infdis/jis232 Copyright (C) 2012, Infectious Diseases Society of America MAJOR ARTICLE TEXT 2012 fthighwire https://doi.org/10.1093/infdis/jis232 2016-11-16T18:51:30Z Background Highly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl, causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 clades is a tremendous challenge for vaccine design. Methods In this study, we generated a synthetic hemagglutinin (HA) on the basis of a new method, computationally optimized broadly reactive antigen (COBRA), which uses worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates. Results Cynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLPs) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades as compared to nonhuman primates vaccinated with clade 2.2 HA VLPs. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge, with no virus detected in the nasal or tracheal washes. However, COBRA VLP–vaccinated nonhuman primates had reduced lung inflammation and pathologic effects as compared to those that received WS/05 VLP vaccines. Conclusions The COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine is more effective than a homologous vaccine against a highly pathogenic avian influenza virus challenge. Text Whooper Swan HighWire Press (Stanford University) The Journal of Infectious Diseases 205 10 1562 1570 |
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MAJOR ARTICLE Giles, Brendan M. Crevar, Corey J. Carter, Donald M. Bissel, Stephanie J. Schultz-Cherry, Stacey Wiley, Clayton A. Ross, Ted M. A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
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MAJOR ARTICLE |
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Background Highly pathogenic H5N1 avian influenza viruses continue to spread via waterfowl, causing lethal infections in humans. Vaccines can prevent the morbidity and mortality associated with pandemic influenza isolates. Predicting the specific isolate that may emerge from the 10 different H5N1 clades is a tremendous challenge for vaccine design. Methods In this study, we generated a synthetic hemagglutinin (HA) on the basis of a new method, computationally optimized broadly reactive antigen (COBRA), which uses worldwide sequencing and surveillance efforts that are specifically focused on sequences from H5N1 clade 2 human isolates. Results Cynomolgus macaques vaccinated with COBRA clade 2 HA H5N1 virus-like particles (VLPs) had hemagglutination-inhibition antibody titers that recognized a broader number of representative isolates from divergent clades as compared to nonhuman primates vaccinated with clade 2.2 HA VLPs. Furthermore, all vaccinated animals were protected from A/Whooper Swan/Mongolia/244/2005 (WS/05) clade 2.2 challenge, with no virus detected in the nasal or tracheal washes. However, COBRA VLP–vaccinated nonhuman primates had reduced lung inflammation and pathologic effects as compared to those that received WS/05 VLP vaccines. Conclusions The COBRA clade 2 HA H5N1 VLP elicits broad humoral immunity against multiple H5N1 isolates from different clades. In addition, the COBRA VLP vaccine is more effective than a homologous vaccine against a highly pathogenic avian influenza virus challenge. |
format |
Text |
author |
Giles, Brendan M. Crevar, Corey J. Carter, Donald M. Bissel, Stephanie J. Schultz-Cherry, Stacey Wiley, Clayton A. Ross, Ted M. |
author_facet |
Giles, Brendan M. Crevar, Corey J. Carter, Donald M. Bissel, Stephanie J. Schultz-Cherry, Stacey Wiley, Clayton A. Ross, Ted M. |
author_sort |
Giles, Brendan M. |
title |
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
title_short |
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
title_full |
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
title_fullStr |
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
title_full_unstemmed |
A Computationally-Optimized Hemagglutinin VLP Vaccine Elicits Broadly-Reactive Antibodies that Protect Non-Human Primates from H5N1 Infection |
title_sort |
computationally-optimized hemagglutinin vlp vaccine elicits broadly-reactive antibodies that protect non-human primates from h5n1 infection |
publisher |
Oxford University Press |
publishDate |
2012 |
url |
http://jid.oxfordjournals.org/cgi/content/short/jis232v1 https://doi.org/10.1093/infdis/jis232 |
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Whooper Swan |
genre_facet |
Whooper Swan |
op_relation |
http://jid.oxfordjournals.org/cgi/content/short/jis232v1 http://dx.doi.org/10.1093/infdis/jis232 |
op_rights |
Copyright (C) 2012, Infectious Diseases Society of America |
op_doi |
https://doi.org/10.1093/infdis/jis232 |
container_title |
The Journal of Infectious Diseases |
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205 |
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10 |
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1562 |
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1570 |
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1766234793232564224 |