Recombinant Vaccine Vector‐Induced Protection of Athymic, Nude Mice from Influenza A Virus Infection. Analysis of Protective Mechanisms
Recombinant Vaccine Vector‐Induced Protection of Athymic, Nude Mice from Influenza A Virus Infection. Analysis of Protective Mechanisms
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重组疫苗载体 - 诱导保护无胸腺裸鼠免受甲型流感病毒感染。
DOI：
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发表时间：
1992
影响因子：
3.7
通讯作者：
R. Blanden
中科院分区：
文献类型：
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作者：
G. Karupiah;A. Ramsay;I. Ramshaw;R. Blanden
裸鼠通常会死于病毒感染，但可以通过重组痘苗病毒表达IL-2。我们已经证明，自然杀伤细胞(NK)和其他免疫细胞产生的干扰素-γ(干扰素-γ)对病毒编码的白介素2(IL-2)的恢复至关重要。在这里，我们扩展这项工作，以表明，当静脉注射共表达IL-2和流感病毒血凝素(HA)基因的rVV时，裸鼠在受到致死剂量的同源流感病毒攻击后也得到保护。在受保护的小鼠的脾和肺中，发现产生IgM同型抗体的流感病毒反应性抗体分泌细胞的数量显著增加，但不产生Ig G或Ig A同型抗体。然而，在攻击时和之后用抗干扰素-γ或NK标志物(如GM1)的单抗治疗会导致它们死亡，尽管特异性IgM抗体反应不受影响。这些数据表明，特异性抗体和非特异性抗病毒反应性都是保护性反应的重要因素，并表明这种免疫策略可用于保护免疫严重受损的个体。
Athymic, nude mice, which normally succumb to virus infection, can resolve infection with recombinant vaccinia virus (rVV) engineered to express IL‐2. We have demonstrated that interferon‐γ (IFN‐γ) produced by natural killer (NK) cells and other immunocytes in response to the virus‐encoded interleukin‐2 (IL‐2) is crucial to recovery. Here, we extend this work to show that nude mice, when primed intravenously with rVV co‐expressing both IL‐2 and an influenza virus haemagglutinin (HA) gene, are also protected following challenge with a lethal dose of homologous influenza virus. A substantial increase in the number of influenza virus‐reactive antibody‐secreting cells producing antibody of the IgM isotype, but not of the IgG or IgA isotypes, was found in spleens and lungs of the protected mice. Treatment with monoclonal antibodies to IFN‐γ or to the NK marker, as GM1, at challenge and thereafter, led to their death however, though the specific IgM antibody response was unaffected. These data suggest that both specific antibody and non‐specific antiviral reactivity are important elements of the protective response and show that this immunization strategy may be used to protect severely immunocompromised individuals.
DOI：
10.1073/pnas.82.6.1785
发表时间：
1985-01-01
影响因子：
11.1
作者：
YEWDELL, JW;BENNINK, JR;MOSS, B
通讯作者：
MOSS, B