Evaluating α-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs.
Evaluating α-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs.
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DOI：
10.1186/s44149-022-00051-x
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发表时间：
2022
期刊：
影响因子：
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中科院分区：
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被糖脂配体α-半乳糖神经酰胺（α-GalCer）激活的自然杀伤T细胞（NKT）刺激多种免疫细胞，增强疫苗介导的免疫反应。一些研究将这种方法用于佐剂灭活疫苗和亚单位甲型流感病毒（IAV）疫苗，包括增强交叉保护性流感免疫。然而，α-GalCer是否能增强减毒流感病毒活疫苗（LAIV）的功能，目前尚不清楚。与非复制型流感疫苗相比，LAIV疫苗通常能诱导更强的异源和异亚型免疫。目前的研究使用猪流感攻击模型来评估α-GalCer是否可以增强重组H3N2 LAIV疫苗（TX98ΔNS1）编码截断的NS1蛋白引发的交叉保护性免疫反应。在一项研究中，断奶仔猪分别接种含有0、10、50和100 μg/kg剂量α-GalCer的H3N2 TX98ΔNS1 LAIV疫苗，随后用异源H3N2病毒攻毒。所有治疗组均未发生感染。然而，α-GalCer的加入似乎抑制了LAIV疫苗的鼻腔脱落。在另一项实验中，接种了H3N2 LAIV的猪，无论是否添加50 μg/kg α-GalCer，都受到异亚型H1N1大流行性流感病毒的攻击。单独接种LAIV的猪产生了交叉反应的体液和细胞反应，阻断了病毒在气道中的复制，并显著减少了病毒的脱落。另一方面，疫苗与α-GalCer联合使用降低了交叉保护性细胞和抗体反应，导致呼吸组织中病毒滴度升高。这些结果表明：(1)高剂量α-GalCer破坏了LAIV疫苗的复制和鼻腔脱落；α-GalCer可能干扰异亚型交叉保护性免疫反应。这项研究提出了在尝试使用NKT细胞激动剂作为LAIV疫苗可能的佐剂方法之前应该考虑的问题。在线版本包含补充资料，下载地址为10.1186/s44149-022-00051-x。
Natural killer T (NKT) cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses. Several studies have used this approach to adjuvant inactivated and subunit influenza A virus (IAV) vaccines, including to enhance cross-protective influenza immunity. However, less is known about whether α-GalCer can enhance live attenuated influenza virus (LAIV) vaccines, which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating influenza vaccines. The current study used the swine influenza challenge model to assess whether α-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine (TX98ΔNS1) encoding a truncated NS1 protein. In one study, weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0, 10, 50, and 100 μg/kg doses of α-GalCer, and subsequently challenged with a heterologous H3N2 virus. All treatment groups were protected from infection. However, the addition of α-GalCer appeared to suppress nasal shedding of the LAIV vaccine. In another experiment, pigs vaccinated with the H3N2 LAIV, with or without 50 μg/kg of α-GalCer, were challenged with the heterosubtypic pandemic H1N1 virus. Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways, and significantly decreased virus shedding. On the other hand, combining the vaccine with α-GalCer reduced cross-protective cellular and antibody responses, and resulted in higher virus titers in respiratory tissues. These findings suggest that: (i) high doses of α-GalCer impair the replication and nasal shedding of the LAIV vaccine; and (ii) α-GalCer might interfere with heterosubtypic cross-protective immune responses. This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines. The online version contains supplementary material available at 10.1186/s44149-022-00051-x.
OX40在肺病毒感染过程中T细胞介导的免疫病理学中的关键作用。
DOI：
10.1084/jem.20030351
发表时间：
2003-10-20
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Humphreys IR;Walzl G;Edwards L;Rae A;Hill S;Hussell T
通讯作者：
Hussell T