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GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-w...

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Autores principales: Clegg, Christopher H., Roque, Richard, Perrone, Lucy A., Rininger, Joseph A., Bowen, Richard, Reed, Steven G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925208/
https://www.ncbi.nlm.nih.gov/pubmed/24551202
http://dx.doi.org/10.1371/journal.pone.0088979
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author Clegg, Christopher H.
Roque, Richard
Perrone, Lucy A.
Rininger, Joseph A.
Bowen, Richard
Reed, Steven G.
author_facet Clegg, Christopher H.
Roque, Richard
Perrone, Lucy A.
Rininger, Joseph A.
Bowen, Richard
Reed, Steven G.
author_sort Clegg, Christopher H.
collection PubMed
description The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.
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spelling pubmed-39252082014-02-18 GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza Clegg, Christopher H. Roque, Richard Perrone, Lucy A. Rininger, Joseph A. Bowen, Richard Reed, Steven G. PLoS One Research Article The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. Public Library of Science 2014-02-14 /pmc/articles/PMC3925208/ /pubmed/24551202 http://dx.doi.org/10.1371/journal.pone.0088979 Text en © 2014 Clegg 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Clegg, Christopher H.
Roque, Richard
Perrone, Lucy A.
Rininger, Joseph A.
Bowen, Richard
Reed, Steven G.
GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title_full GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title_fullStr GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title_full_unstemmed GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title_short GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza
title_sort gla-af, an emulsion-free vaccine adjuvant for pandemic influenza
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925208/
https://www.ncbi.nlm.nih.gov/pubmed/24551202
http://dx.doi.org/10.1371/journal.pone.0088979
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