Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.

Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.
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DOI:
10.1371/journal.pone.0079194
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Palese P
Palese P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Goff PH;Eggink D;Seibert CW;Hai R;Martínez-Gil L;Krammer F;Palese P

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面对下一次大流行性流感病毒爆发,全球人口仍然很脆弱,每年都要进行重新配制的疫苗接种,以控制季节性流行病。因此,需要开发新一代疫苗以产生对流感病毒的广泛和持久的免疫力。在这里,我们描述了三种佐剂,当与嵌合HA蛋白一起施用时,其增强针对异源和异亚型流感病毒的茎导向抗体的诱导。Addavax、MF59样纳米乳剂、poly(I:C)和来自仙台病毒(SeV)Cantell的RNA发夹肌内注射是有效的。SeV RNA和poly(I:C)也被证明是有效的呼吸道粘膜佐剂。尽管佐剂诱导的抗体的数量和质量不同,但基于HA茎反应性,免疫小鼠表现出相当水平的针对甲型流感病毒攻击的保护。最后,我们提出,鼻内,但不是肌肉注射,给予嵌合HA蛋白诱导粘膜伊加抗体针对HA柄。
The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk-directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C), and an RNA hairpin derived from Sendai virus (SeV) Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C) also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk.
DOI: 10.1371/journal.pone.0043603
发表时间: 2012
期刊: PloS one
影响因子: 3.7
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