A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia.
A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia.
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一种基于 PB2 敲除流感病毒的二价疫苗可保护小鼠免受继发性肺炎球菌肺炎的侵害。
DOI：
10.1093/infdis/jiv341
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发表时间：
2015
期刊：
影响因子：
6.4
通讯作者：
Kawaoka Y.
中科院分区：
文献类型：
--
作者：
Uraki R;Piao Z;Akeda Y;Iwatsuki-Horimoto K;Kiso M;Ozawa M;Oishi K;Kawaoka Y.
背景：流感后继发性细菌感染是一个严重的问题，特别是在幼儿和老年人中，然而目前疫苗的有效性有限。早期的工作表明，一个复制能力PB 2敲除（PB 2-KO）流感病毒在其PB 2片段的编码区具有外源基因可以作为一个平台的二价疫苗。方法。在目前的研究中，我们产生的PB 2-KO病毒表达肺炎球菌表面蛋白A（PspA），PB 2-KO-PspA病毒，其复制仅限于PB 2表达细胞。然后，我们研究了鼻内免疫与此病毒作为一种双价疫苗在小鼠model.Results的保护效力。流感病毒特异性和PspA特异性抗体的高水平诱导免疫小鼠的血清和气道。鼻内免疫的小鼠对致死剂量的流感病毒或肺炎链球菌有保护作用，这些小鼠也对流感病毒感染后继发的肺炎球菌肺炎有完全的保护作用。
Background.Secondary bacterial infections after influenza can be a serious problem, especially in young children and the elderly, yet the efficacy of current vaccines is limited. Earlier work demonstrated that a replication-incompetent PB2-knockout (PB2-KO) influenza virus possessing a foreign gene in the coding region of its PB2 segment can serve as a platform for a bivalent vaccine.Methods.In the current study, we generated the PB2-KO virus expressing pneumococcal surface protein A (PspA), PB2-KO-PspA virus, the replication of which is restricted to PB2-expressing cells. We then examined the protective efficacy of intranasal immunization with this virus as a bivalent vaccine in a mouse model.Results.High levels of influenza virus–specific and PspA-specific antibodies were induced in the serum and airways of immunized mice. The intranasally immunized mice were protected from lethal doses of influenza virus orStreptococcus pneumoniae.These mice were also completely protected from secondary pneumococcal pneumonia after influenza virus infection.Conclusions.These findings indicate that our recombinant influenza virus serves as a novel and powerful bivalent vaccine against primary and secondary pneumococcal pneumonia as well as influenza.
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