BIOLOGICAL-ACTIVITY OF MONOCLONAL-ANTIBODIES TO OPERATIONALLY DEFINED ANTIGENIC REGIONS ON THE HEMAGGLUTININ MOLECULE OF A/SEAL MASSACHUSETTS/1/80 (H7N7) INFLUENZA-VIRUS
BIOLOGICAL-ACTIVITY OF MONOCLONAL-ANTIBODIES TO OPERATIONALLY DEFINED ANTIGENIC REGIONS ON THE HEMAGGLUTININ MOLECULE OF A/SEAL MASSACHUSETTS/1/80 (H7N7) INFLUENZA-VIRUS
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DOI：
10.1016/0042-6822(82)90375-0
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发表时间：
1982-01-01
期刊：
影响因子：
3.7
通讯作者：
WEBSTER, RG
中科院分区：
文献类型：
--
作者：
KIDA, H;BROWN, LE;WEBSTER, RG
制备A/Seal/Mass/1/80 （H7N7）血凝素（HA）分子小鼠单克隆抗体，建立可操作的抗原图谱。在海豹流感病毒HA上确定了4个不重叠的抗原区。其中2组（III和IV）单克隆抗体不能抑制完整病毒的血凝，但能有效中和病毒的感染性。这些发现不能用亲和度的差异来解释，而是用两种测定方法之间的功能差异来解释。不能抑制血凝的抗体可能更靠近HA分子的疏水端结合，可能不会阻断红细胞的受体结合位点。这些区域的抗体可以通过干扰细胞融合或病毒复制来抑制传染性。单克隆抗体不能抑制完整病毒的血凝，但却能抑制纯化的血凝素玫瑰花的HA活性。抑制的机制尚不清楚，但可能涉及到与位于病毒膜上的HA相比，当HA以玫瑰花的形式存在时，大量抗体分子可以接近HA。这些单克隆抗体对海豹流感病毒和其他禽类H7病毒的反应性表明，一些禽类毒株具有与海豹病毒密切相关的HA分子，因此可能与在该毒株进化中起重要作用的病毒有关。由于血凝抑制试验不一定能检测到所有中和病毒传染性的抗体，因此提出了一个问题，即血凝抑制试验是否可以单独用于确定所有流感病毒疫苗的效力。
Mouse monoclonal antibodies to the hemagglutinin (HA) molecule of A/Seal/Mass/1/80 (H7N7) were prepared and used to establish an operational antigenic map. Four nonoverlapping antigenic areas on the HA of seal influenza viruses were defined. Monoclonal antibodies belonging to 2 of the groups (III and IV) failed to inhibit hemagglutination of intact virus yet effectively neutralized viral infectivity. These findings could not be explained by differences in affinities and were interpreted in terms of functional differences between the assays. Antibodies that failed to inhibit hemagglutination may bind nearer to the hydrophobic end of the HA molecule and might not block the receptor binding site for erythrocytes. Antibodies to these areas may inhibit infectivity by interference with cell fusion or viral replication. The monoclonal antibodies that failed to inhibit hemagglutination of intact virus nevertheless did inhibit HA activity of purified isolated rosettes of hemagglutinin. The mechanism of inhibition is not resolved but may involve the access of a large number of antibody molecules to the HA when it is in the form of rosettes compared to when it is located on the viral membrane. The reactivity of seal influenza virus and other H7 viruses from birds with the monoclonal antibodies show that some avian strains possess HA molecules that are closely related to those of seal virus and may therefore be related to viruses that were important in the evolution of this strain. Since hemagglutination-inhibition [HI] tests do not necessarily detect all antibodies that neutralize viral infectivity, the question is raised as to whether HI assays alone can be used for determining the efficacy of all influenza virus vaccines.