A Synthetic Adjuvant to Enhance and Expand Immune Responses to Influenza Vaccines

被引：119

作者：

Coler, Rhea N. ^{[1
]}

Baldwin, Susan L. ^{[1
]}

Shaverdian, Narek ^{[1
]}

Bertholet, Sylvie ^{[1
]}

Reed, Steven J. ^{[1
]}

Raman, Vanitha S. ^{[1
]}

Lu, Xiuhua ^{[2
]}

DeVos, Joshua ^{[2
]}

Hancock, Kathy ^{[2
]}

Katz, Jacqueline M. ^{[2
]}

Vedvick, Thomas S. ^{[1
]}

Duthie, Malcolm S. ^{[1
]}

Clegg, Christopher H. ^{[3
]}

Van Hoeven, Neal ^{[3
]}

Reed, Steven G. ^{[1
,3
]}

机构：

[1] Infect Dis Res Inst, Seattle, WA USA

[2] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA

[3] Immune Design Corp, Seattle, WA USA

来源：

PLOS ONE | 2010年 / 5卷 / 10期

基金：

美国国家卫生研究院;

关键词：

T-CELL RESPONSES; IN-VIVO; ANTIBODY; AGE; VACCINATION; INFECTION; EMULSION; ADULTS; TRIAL; MICE;

D O I：

10.1371/journal.pone.0013677

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Safe, effective adjuvants that enhance vaccine potency, including induction of neutralizing Abs against a broad range of variant strains, is an important strategy for the development of seasonal influenza vaccines which can provide optimal protection, even during seasons when available vaccines are not well matched to circulating viruses. We investigated the safety and ability of Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE), a synthetic Toll-like receptor (TLR) 4 agonist formulation, to adjuvant Fluzone(R) in mice and non-human primates. The GLA-SE adjuvanted Fluzone vaccine caused no adverse reactions, increased the induction of T helper type 1 (TH1)-biased cytokines such as IFN gamma, TNF and IL-2, and broadened serological responses against drifted A/H1N1 and A/H3N2 influenza variants. These results suggest that synthetic TLR4 adjuvants can enhance the magnitude and quality of protective immunity induced by influenza vaccines.

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页数：11

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共 32 条

[1] TLR4 agonists as immunomodulatory agents [J].

Alderson, Mark R. ;

McGowan, Patrick ;

Baldridge, Jory R. ;

Probst, Peter .

JOURNAL OF ENDOTOXIN RESEARCH, 2006, 12 (05) :313-319

[2] Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations [J].

Anderson, Ryan C. ;

Fox, Christopher B. ;

Dutill, Timothy S. ;

Shaverdian, Narek ;

Evers, Tara L. ;

Poshusta, Garrett R. ;

Chesko, James ;

Coler, Rhea N. ;

Friede, Martin ;

Reed, Steven G. ;

Vedvick, Thomas S. .

COLLOIDS AND SURFACES B-BIOINTERFACES, 2010, 75 (01) :123-132

[3] Enhanced humoral and Type 1 cellular immune responses with Fluzone® adjuvanted with a synthetic TLR4 agonist formulated in an emulsion [J].

Baldwin, Susan L. ;

Shaverdian, Narek ;

Goto, Yasuyuki ;

Duthie, Malcolm S. ;

Raman, Vanitha S. ;

Evers, Tara ;

Mompoint, Farah ;

Vedvick, Thomas S. ;

Bertholet, Sylvie ;

Coler, Rhea N. ;

Reed, Steven G. .

VACCINE, 2009, 27 (43) :5956-5963

[4] Intradermal immunization improves protective efficacy of a novel TB vaccine candidate [J].

Baldwin, Susan L. ;

Bertholet, Sylvie ;

Kahn, Maria ;

Zharkikh, Irina ;

Ireton, Gregory C. ;

Vedvick, Thomas S. ;

Reed, Steven G. ;

Coler, Rhea N. .

VACCINE, 2009, 27 (23) :3063-3071

[5] A new MF59-adjuvanted influenza vaccine enhances the immune response in the elderly with chronic diseases: Results from an immunogenicity meta-analysis [J].

Banzhoff, A ;

Nacci, P ;

Podda, A .

GERONTOLOGY, 2003, 49 (03) :177-184

[6] Epidemiological, antigenic and genetic characteristics of seasonal influenza A(H1N1), A(H3N2) and B influenza viruses: Basis for the WHO recommendation on the composition of influenza vaccines for use in the 2009-2010 Northern Hemisphere season [J].

Barr, Ian G. ;

McCauley, John ;

Cox, Nancy ;

Daniels, Rod ;

Engelhardt, Othmar G. ;

Fukuda, Keiji ;

Grohmann, Gary ;

Hay, Alan ;

Kelso, Anne ;

Klimov, Alexander ;

Odagiri, Takato ;

Smith, Derek ;

Russell, Colin ;

Tashiro, Masato ;

Webby, Richard ;

Wood, John ;

Ye, Zhiping ;

Zhang, Wenqing .

VACCINE, 2010, 28 (05) :1156-1167

[7] MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020) [J].

Baudner, Barbara C. ;

Ronconi, Vanessa ;

Casini, Daniele ;

Tortoli, Marco ;

Kazzaz, Jina ;

Singh, Manmohan ;

Hawkins, Lynn D. ;

Wack, Andreas ;

O'Hagan, Derek T. .

PHARMACEUTICAL RESEARCH, 2009, 26 (06) :1477-1485

[8] In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the focal cellular immune response in lung tissue [J].

Baumgarth, N ;

Kelso, A .

JOURNAL OF VIROLOGY, 1996, 70 (07) :4411-4418

[9] Compromised influenza virus-specific CD8+-T-Cell memory in CD4+-T-cell-deficient mice [J].

Belz, GT ;

Wodarz, D ;

Diaz, G ;

Nowak, MA ;

Doherty, PC .

JOURNAL OF VIROLOGY, 2002, 76 (23) :12388-12393

[10] Effectiveness and cost-benefit of influenza vaccination of healthy working adults - A randomized controlled trial [J].

Bridges, CB ;

Thompson, WW ;

Meltzer, MI ;

Reeve, GR ;

Talamonti, WJ ;

Cox, NJ ;

Lilac, HA ;

Hall, H ;

Klimov, A ;

Fukuda, K .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 284 (13) :1655-1663

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