GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.
GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.
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DOI：
10.1371/journal.pone.0088979
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Reed SG
中科院分区：
文献类型：
--
作者：
Clegg CH;Roque R;Perrone LA;Rininger JA;Bowen R;Reed SG
流感的持续威胁需要开发新的疫苗和佐剂技术，以最大限度地提高疫苗的免疫原性、缩短生产周期并增加全球疫苗供应。目前，最成功的流感疫苗佐剂是基于角鲨烯的水包油乳液。这些佐剂增强了对同源和异源病毒株的血清保护性抗体滴度，并增强了显着的剂量节省活性，从而提高了疫苗的生产能力。作为乳剂的替代品，我们测试了一种含有合成 TLR4 配体 (GLA-AF) 的简单脂质基水制剂，以了解其增强针对 H5N1 感染的保护能力。 GLA-AF 在小鼠体内辅助重组 H5 血凝素抗原 (rH5) 非常有效，并且与稳定乳液 SE 一样有效。两种佐剂均使用亚微克剂量的 rH5 诱导相似的抗体滴度，并且均能针对高致病性 H5N1 攻击提供完全保护。然而，GLA-AF 是雪貂的最佳佐剂。在使用 rH5 进行初次免疫和加强免疫后，GLA-AF 比 SE 刺激了更广泛的抗体反应，并且雪貂能够更好地免受 H5N1 病毒的同源和异源毒株的侵害。因此，GLA-AF 是一种有效的无乳剂佐剂，值得在大流行性流感疫苗开发中考虑。
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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DOI：
10.1136/bmj.f4752
发表时间：
2013-08-06
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Qi X;Qian YH;Bao CJ;Guo XL;Cui LB;Tang FY;Ji H;Huang Y;Cai PQ;Lu B;Xu K;Shi C;Zhu FC;Zhou MH;Wang H
通讯作者：
Wang H
DOI：
10.1073/pnas.0903181106
发表时间：
2009-05-12
影响因子：
11.1
作者：
Galli, Grazia;Hancock, Kathy;Stephenson, Iain
通讯作者：
Stephenson, Iain
影响因子：
5.8
作者：
Anderson, Ryan C.;Fox, Christopher B.;Vedvick, Thomas S.
通讯作者：
Vedvick, Thomas S.
影响因子：
11.5
作者：
McKeage, Kate;Romanowski, Barbara
通讯作者：
Romanowski, Barbara
影响因子：
4.3
作者：
Belser JA;Katz JM;Tumpey TM
通讯作者：
Tumpey TM