CD40-mediated enhancement of immune responses against three forms of influenza vaccine
CD40-mediated enhancement of immune responses against three forms of influenza vaccine
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DOI：
10.1111/j.1365-2567.2007.02617.x
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发表时间：
2007-09-01
期刊：
影响因子：
6.4
通讯作者：
Heath, Andrew W.
中科院分区：
文献类型：
--
作者：
Hatzifoti, Caterina;Heath, Andrew W.
甲型流感感染有可能造成大量发病率和死亡率。疫苗接种可能是针对大流行性流感的主要防御措施，潜在的大流行性流感疫苗可能以常规方式在胚胎蛋中生产，或作为重组蛋白或合成肽疫苗生产。无论疫苗是如何生产的，其供应可能是有限的，因此尽可能提高疫苗的免疫原性是很重要的。我们已经证明与CD40结合抗体结合是一种非常有效的增强针对模型抗原的免疫反应的方法，但我们对评估该系统使用流感疫苗的有效性感兴趣。我们用三种潜在的流感疫苗制备了CD40单克隆抗体（mAb）和同型对照的偶联物：一种基于肽的疫苗，含有来自病毒血凝素的t和b细胞表位；一个完整的灭活病毒疫苗；以及商业化生产的分裂病毒疫苗。CD40单抗结合物在每种情况下都具有更强的免疫原性，但CD40结合物的佐剂作用在分裂疫苗中最大，在单次免疫后抗体反应增强了数百倍，并且体外淋巴细胞对抗原的反应也得到了强烈增强。甲型流感感染有可能造成大量发病率和死亡率。疫苗接种可能是针对大流行性流感的主要防御措施，潜在的大流行性流感疫苗可能以常规方式在胚胎蛋中生产，或作为重组蛋白或合成肽疫苗生产。无论疫苗是如何生产的，其供应可能是有限的，因此尽可能提高疫苗的免疫原性是很重要的。我们已经证明与CD40结合抗体结合是一种非常有效的增强针对模型抗原的免疫反应的方法，但我们对评估该系统使用流感疫苗的有效性感兴趣。我们用三种潜在的流感疫苗制备了CD40单克隆抗体（mAb）和同型对照的偶联物：一种基于肽的疫苗，含有来自病毒血凝素的t和b细胞表位；一个完整的灭活病毒疫苗；以及商业化生产的分裂病毒疫苗。CD40单抗结合物在每种情况下都具有更强的免疫原性，但CD40结合物的佐剂作用在分裂疫苗中最大，在单次免疫后抗体反应增强了数百倍，并且体外淋巴细胞对抗原的反应也得到了强烈增强。
There is potential for influenza A infections to cause massive morbidity and mortality. Vaccination may be the primary defence against pandemic influenza, and potential pandemic'flu vaccines may be produced conventionally, in embryonated eggs, or as recombinant protein or synthetic peptide vaccines. However the vaccines are produced, the supply may be limiting, and it will be important to enhance the immunogenicity of the vaccines as much as possible. We have shown that conjugation to CD40 binding antibody is a very efficient way of enhancing immune responses against model antigens, but were interested in assessing the effectiveness of this system using influenza vaccines. We produced conjugates of CD40 monoclonal antibody ( mAb) and isotype control with three potential influenza vaccines: a peptide-based vaccine containing T-and B-cell epitopes from virus haemagglutinin; a whole, killed virus vaccine; and a commercially produced split virus vaccine. CD40 mAb conjugates in each case were more immunogenic, but the adjuvant effect of CD40 conjugation was greatest with the split vaccine, where antibody responses were enhanced by several hundred-fold after a single immunization, and lymphocyte proliferation in response to antigen in vitro was also strongly enhanced. There is potential for influenza A infections to cause massive morbidity and mortality. Vaccination may be the primary defence against pandemic influenza, and potential pandemic'flu vaccines may be produced conventionally, in embryonated eggs, or as recombinant protein or synthetic peptide vaccines. However the vaccines are produced, the supply may be limiting, and it will be important to enhance the immunogenicity of the vaccines as much as possible. We have shown that conjugation to CD40 binding antibody is a very efficient way of enhancing immune responses against model antigens, but were interested in assessing the effectiveness of this system using influenza vaccines. We produced conjugates of CD40 monoclonal antibody (mAb) and isotype control with three potential influenza vaccines: a peptide-based vaccine containing T-and B-cell epitopes from virus haemagglutinin; a whole, killed virus vaccine; and a commercially produced split virus vaccine. CD40 mAb conjugates in each case were more immunogenic, but the adjuvant effect of CD40 conjugation was greatest with the split vaccine, where antibody responses were enhanced by several hundred-fold after a single immunization, and lymphocyte proliferation in response to antigen in vitro was also strongly enhanced.