Live attenuated influenza vaccine (LAIV) impacts innate and adaptive immune responses.
Live attenuated influenza vaccine (LAIV) impacts innate and adaptive immune responses.
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DOI：
10.1016/j.vaccine.2011.07.093
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发表时间：
2011-10-13
期刊：
影响因子：
5.5
通讯作者：
Haynes, Laura
中科院分区：
文献类型：
--
作者：
Lanthier, Paula A.;Huston, Gail E.;Moquin, Amy;Eaton, Sheri M.;Szaba, Frank M.;Kummer, Lawrence W.;Tighe, Micheal P.;Kohlmeier, Jacob E.;Blair, Patrick J.;Broderick, Michael;Smiley, Stephen T.;Haynes, Laura
甲型流感感染在肺部引起大量炎症反应，导致严重疾病并增加继发性细菌性肺炎的易感性。预防流感最有效的方法是接种疫苗。虽然灭活疫苗诱导针对流感血凝素（HA）和神经氨酸酶（NA）表面蛋白的血清抗体达到保护水平，但这些抗体具有毒株特异性，对异亚型流感病毒几乎没有保护作用。相反，减毒活流感疫苗（LAIV）除了诱导针对HA和NA表面蛋白的抗体应答之外还诱导T细胞应答。重要的是，LAIV疫苗接种在小鼠模型中诱导了一种应答，该应答可防止由于异亚型流感毒株引起的疾病。虽然尚不完全清楚LAIV在人类中的异亚型保护作用的机制是什么，但已显示LAIV在小鼠中诱导异亚型保护，其依赖于1型免疫应答并需要CD8 T细胞。在这项研究中，我们表明，LAIV诱导的免疫导致显着降低病毒滴度和炎症反应，在肺部的小鼠异亚型感染。LAIV疫苗接种的小鼠不仅病毒滴度降低，肺组织中炎性细胞因子和趋化因子的量也显著降低。此外，我们表明，健康成人的LAIV疫苗接种也诱导了强大的1型记忆反应，包括参与T细胞活化和募集的趋化因子和细胞因子的产生。因此，我们的研究结果表明，LAIV疫苗接种的功能，诱导免疫记忆，可以发挥作用，以调节免疫反应，随后的异亚型的挑战，通过影响先天性和适应性反应。
Influenza A infection induces a massive inflammatory response in the lungs that leads to significant illness and increases the susceptibility to secondary bacterial pneumonia. The most efficient way to prevent influenza infection is through vaccination. While inactivated vaccines induce protective levels of serum antibodies to influenza hemaglutinin (HA) and neuraminidase (NA) surface proteins, these are strain specific and offer little protection against heterosubtypic influenza viruses. In contrast, live attenuated influenza vaccines (LAIVs) induce a T cell response in addition to antibody responses against HA and NA surface proteins. Importantly, LAIV vaccination induces a response in a mouse model that protects against illness due to heterosubtypic influenza strains. While it is not completely clear what is the mechanism of action of LAIV heterosubtypic protection in humans, it has been shown that LAIV induces heterosubtypic protection in mice that is dependent upon a Type 1 immune response and requires CD8 T cells. In this study, we show that LAIV-induced immunity leads to significantly reduced viral titers and inflammatory responses in the lungs of mice following heterosubtypic infection. Not only are viral titers reduced in LAIV vaccinated mice, the amounts of inflammatory cytokines and chemokines in lung tissue are significantly lower. Additionally, we show that LAIV vaccination of healthy adults also induces a robust Type 1 memory response including the production of chemokines and cytokines involved in T cell activation and recruitment. Thus, our results indicate that LAIV vaccination functions by inducing immune memory which can act to modulate the immune response to subsequent heterosubtypic challenge by influencing both innate and adaptive responses.
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作者：
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