The effects of preexisting immunity to influenza on responses to influenza vectors in mice.
The effects of preexisting immunity to influenza on responses to influenza vectors in mice.
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DOI：
10.1016/j.vaccine.2010.06.112
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发表时间：
2010-08
期刊：
影响因子：
5.5
通讯作者：
William A. Langley;Konrad C. Bradley;Zhu-Nan Li;G. Talekar;Summer E. Galloway;D. Steinhauer
中科院分区：
文献类型：
--
作者：
William A. Langley;Konrad C. Bradley;Zhu-Nan Li;G. Talekar;Summer E. Galloway;D. Steinhauer
使用病毒载体作为候选疫苗已经显示出对抗许多病原体的希望。然而，在决定哪些病毒适合使用时，必须考虑对这些载体的预先存在的免疫力。许多特性，包括抗原性不同亚型的存在，使得流感病毒成为用作病毒载体的有吸引力的候选者。在这里，我们评估的能力，流感病毒载体含有插入的外来病原体引发抗体和CD8+T细胞对这些外来抗原的免疫存在下，在小鼠中的流感病毒。具体地，在用同型亚型或异型亚型流感病毒感染后，评价了对表达源自炭疽芽孢杆菌保护性抗原（PA）的90个氨基酸多肽的基于H3N1的载体或含有来自淋巴细胞性脉络丛脑膜炎病毒糖蛋白（GP）的CD8+T细胞表位的基于H1N1的载体的应答。我们发现，先前感染流感病毒的小鼠，即使是那些表达完全不同亚型的HA和NA蛋白的小鼠，对插入的表位产生免疫应答的能力也严重受损。这种抑制被证明是由CD8+T细胞介导的，其识别多种流感病毒株。这些CD8+T细胞进一步显示出保护小鼠免受异源流感亚型的致死性攻击。这些数据的使用流感病毒载体和流感疫苗接种一般的含义进行了讨论。
The use of viral vectors as vaccine candidates has shown promise against a number of pathogens. However, preexisting immunity to these vectors is a concern that must be addressed when deciding which viruses are suitable for use. A number of properties, including the existence of antigenically distinct subtypes, make influenza viruses attractive candidates for use as viral vectors. Here, we evaluate the ability of influenza viral vectors containing inserts of foreign pathogens to elicit antibody and CD8+T cell responses against these foreign antigens in the presence of preexisting immunity to influenza virus in mice. Specifically, responses to an H3N1-based vector expressing a 90 amino acid polypeptide derived from the protective antigen (PA) of Bacillus anthracis or an H1N1-based vector containing a CD8+T cell epitope from the glycoprotein (GP) of lymphocytic choriomeningitis virus were evaluated following infections with either homosubtypic or heterosubtypic influenza viruses. We found that mice previously infected with influenza viruses, even those expressing HA and NA proteins of completely different subtypes, were severely compromised in their ability to mount an immune response against the inserted epitopes. This inhibition was demonstrated to be mediated by CD8+T cells, which recognize multiple strains of influenza viruses. These CD8+T cells were further shown to protect mice from a lethal challenge by a heterologous influenza subtype. The implication of these data for the use of influenza virus vectors and influenza vaccination in general are discussed.