Adjuvant solution for pandemic influenza vaccine production

被引:62
作者
Clegg, Christopher H. [1 ]
Roque, Richard [1 ]
Van Hoeven, Neal [2 ]
Perrone, Lucy [1 ]
Baldwin, Susan L. [2 ]
Rininger, Joseph A. [3 ]
Bowen, Richard A. [4 ]
Reed, Steven G. [2 ,5 ]
机构
[1] TRIA Biosci Corp, Seattle, WA 98104 USA
[2] Infect Dis Res Inst, Seattle, WA 98104 USA
[3] Prot Sci Corp, Meriden, CT 06450 USA
[4] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA
[5] Immune Design Corp, Seattle, WA 98104 USA
基金
美国国家卫生研究院;
关键词
CELL RESPONSE; VIRUS; MICE; MF59; IMMUNOGENICITY; EMULSION; IMMUNITY; SAFETY; ROLES;
D O I
10.1073/pnas.1207308109
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
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 sub-microgram 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.
引用
收藏
页码:17585 / 17590
页数:6
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