Giuseppe
Emeritus
[Source: Proceedings of the National Academy of the Sciences of the United States of America, full text: (LINK). Abstract, edited.]
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Adjuvant solution for pandemic influenza vaccine production
Christopher H. Clegg<SUP>a</SUP>,<SUP>1</SUP>, Richard Roque<SUP>a</SUP>, Neal Van Hoeven<SUP>b</SUP>, Lucy Perrone<SUP>a</SUP>, Susan L. Baldwin<SUP>b</SUP>, Joseph A. Rininger<SUP>c</SUP>, Richard A. Bowen<SUP>d</SUP>, and Steven G. Reed<SUP>b</SUP>,<SUP>e</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>TRIA Bioscience Corp., Seattle, WA 98104; <SUP>b</SUP>Infectious Disease Research Institute, Seattle, WA 98104; <SUP>c</SUP>Protein Sciences Corporation, Meriden, CT 06450; <SUP>d</SUP>Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523; and <SUP>e</SUP>Immune Design Corp., Seattle, WA 98104
Edited by Barry R. Bloom, Harvard School of Public Health, Boston, MA, and approved September 10, 2012 (received for review May 1, 2012)
Abstract
Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.
Footnotes
<SUP>1</SUP>To whom correspondence should be addressed. E-mail: cclegg@triabio.com.
Author contributions: C.H.C., N.V.H., L.P., S.L.B., R.A.B., and S.G.R. designed research; R.R., N.V.H., L.P., and R.A.B. performed research; J.A.R. contributed new reagents/analytic tools; C.H.C., R.R., N.V.H., L.P., and S.L.B. analyzed data; and C.H.C. and S.G.R. wrote the paper.
Conflict of interest statement: C.H.C. is a full-time employee of TRIA Bioscience, is a consultant for Immune Design Corp., and has equity in Immune Design; N.V.H. has equity in Immune Design; J.A.R. was a full-time employee of Protein Sciences Corp.; and S.G.R. is an inventor on GLA patents licensed by Immune Design and has equity in Immune Design.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1207308109/-/DCSupplemental.
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Author Affiliations: <SUP>a</SUP>TRIA Bioscience Corp., Seattle, WA 98104; <SUP>b</SUP>Infectious Disease Research Institute, Seattle, WA 98104; <SUP>c</SUP>Protein Sciences Corporation, Meriden, CT 06450; <SUP>d</SUP>Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523; and <SUP>e</SUP>Immune Design Corp., Seattle, WA 98104
Edited by Barry R. Bloom, Harvard School of Public Health, Boston, MA, and approved September 10, 2012 (received for review May 1, 2012)
Abstract
Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.
Footnotes
<SUP>1</SUP>To whom correspondence should be addressed. E-mail: cclegg@triabio.com.
Author contributions: C.H.C., N.V.H., L.P., S.L.B., R.A.B., and S.G.R. designed research; R.R., N.V.H., L.P., and R.A.B. performed research; J.A.R. contributed new reagents/analytic tools; C.H.C., R.R., N.V.H., L.P., and S.L.B. analyzed data; and C.H.C. and S.G.R. wrote the paper.
Conflict of interest statement: C.H.C. is a full-time employee of TRIA Bioscience, is a consultant for Immune Design Corp., and has equity in Immune Design; N.V.H. has equity in Immune Design; J.A.R. was a full-time employee of Protein Sciences Corp.; and S.G.R. is an inventor on GLA patents licensed by Immune Design and has equity in Immune Design.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1207308109/-/DCSupplemental.
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