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首页> 外文期刊>Vaccine >Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine
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Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine

机译:新型G3 / DT佐剂在接种季节性三价灭活分裂病毒流感疫苗后可促进保护性T细胞应答的诱导

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Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8(+) T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses
机译:抗季节性流感的疫苗对可能具有大流行潜力的新型亚型A型流感病毒效果不佳。此外,大流行前流感疫苗的免疫原性很差,可以通过使用佐剂来克服。已经批准了有限数量的佐剂用于人类,但是需要替代的安全有效的佐剂,它们可以增强流感疫苗的免疫原性并促进诱导广泛保护性T细胞应答。在这里,我们评估了一种新型的纳米粒子G3作为小鼠模型中季节性三价灭活流感疫苗的佐剂。 G3佐剂配制有或没有甜菊糖苷(DT,代表二萜)。两种制剂的使用都大大增强了对所有三种疫苗株的病毒特异性抗体应答。佐剂耐受良好,没有任何不适的迹象。为了评估疫苗诱导的免疫反应的保护潜力,将抗原性不同的流感病毒株A / Puerto Rico / 8/34(A / PR / 8/34)用于激发感染。在HI和VN分析中,疫苗诱导的抗体不会与菌株A / PR / 8/34交叉反应。但是,用G3 / DT佐剂疫苗免疫的小鼠受到了部分保护,免于A / PR / 8/34感染,这与诱导记忆蛋白特异性CD8(+)T细胞应答有关,而使用A3并未观察到没有DT的G3。两种制剂都诱导人树突状细胞的成熟并以相似的程度促进抗原呈递。总之,G3 / DT是一种很有前途的佐剂制剂,它不仅可以增强流感疫苗诱导的抗体反应,还可以诱导T细胞免疫,从而可以提供针对抗原性不同的流感病毒的更广泛保护

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