Primary Study of the Universal Influenza Vaccine that Images Viral Receptor

本项目主要研究开发通用流感疫苗，该疫苗广泛有效，与针对流感病毒受体抗体的抗独特型抗体相关的病毒血凝素基因变异无关，在本研究过程中，1）建立了一种新的测定流感病毒变异株受体特异性的方法。该方法是基于病毒与唾液酸鞘脂（神经节苷脂）或唾液酸辅蛋白的结合。2）建立了流感病毒受体神经节苷脂的简单分级分离方法。该方法基于使用新的阴离子交换珠（Q-sepharose）通过色谱法对神经节苷脂种类进行作图。 ...更多信息 H1 - H13亚型病毒血凝素测定。发现NeuAcalpha 2，3（6）Galbeta 1，3（6）GlcNAc beta1-是所有血凝素亚型共同识别的最活跃的受体决定簇。血红蛋白在NeuAc和Gal间的连锁中的表达α 2，3和α 2，6不总是依赖于226位氨基酸4）位于远离受体结合口袋的Ser（205）的单个氨基酸取代，A/Mem/1/71-Bel/42（H3 N1）的抗原位点D，与Tyr的结合将受体结合特异性从2，3改变为2，6。Ser（205）位于受体结合位点的亚基界面上。5）制备了一种针对甲型流感病毒常见受体神经节苷脂（NeuAcalpha 2，3Galbeta 1，4GlcNAc beta1，3Galbeta 1，4Glc beta1-Ceramide）的单克隆抗体（NS 24）。该抗体对唾液酸副糖苷的NeuAc 2，3Gal 1，4GlcNAc 1-残基具有高度特异性，并能抑制A病毒与唾液酸酶处理后再用唾液酸副糖苷重组的红细胞的结合。该抗体可用作对流感病毒血凝素的多种亚型有效的通用流感疫苗。6）关于针对针对流感病毒受体的抗体唾液酸副球糖苷的抗独特型抗体，讨论了开发通用流感病毒疫苗的策略。7）流感病毒神经氨酸酶的新的共同竞争性抑制剂，发现神经节苷脂含有NeuAc和Gal之间的硫代糖苷键。

This project is aimed to study primarily the developing the universal influenza vaccine, which is widely effective, independent of the variation of the viral hemagglutinin gene in relation to the anti-idiotypic antibody against the antibody directed to the influenza virus receptor.During the course of this study, following new results were obtained.1) A new simple and improved assay method to determine the receptor specificity of influenza virus variant has been developed. This method is based on the binding of the virus to the sialoglycosphingolipids (gangliosides) or sialogly-coprotein developed in silica gel thin layer plate or film blotted from the gel after electrophoresis.2) The simple method for the fractionation and isolation of receptor gangliosides for influenza viruses was developed. This method is based on the mapping the ganglioside species by chromatography using a new anion exchange beads (Q-sepharose).3) ALL the base sequences of the gene and the receptor specificity of … More viral hemagglutinin subtype (H1 - H13) were determined. It was found that NeuAcalpha2, 3 (6) Galbeta1, 3 (6) GlcNAcbeta1- is the most active receptor determinant which is commonly recognized by all the hemagglutin subtypes. The recogn ition of the hemadgglutinin the linkage between NeuAc and Gal (alpha2, 3 and alpha2, 6) was not always depend on the amino acid 226 (Leu or Gln) in the receptor binding pocket in the hemagglutinin molecule.4) Single amino acid substitution of Ser (205) located distant from the receptor binding pocket, antigenic site D of A/Mem/1/71-Bel/42 (H3N1), to Tyr changed the receptor binding specificity from 2, 3 to 2, 6. Ser (205) is located across the subunit interface from the receptor-binding site. The bultky hydrophobic tyr in the variant may cause a conformational change in the receptor-binding pocket on the neighboring subunit and influence the receptor binding.5) A new monoclonal antibody (NS24) directed to sialylparagloboside (NeuAcalpha2, 3Galbeta1, 4GlcNAcbeta1, 3Galbeta1, 4Glcbeta1-Ceramide), a common receptor gangioside of influenza A viruses was prepared. This antibody was highly specific toNeuAc2, 3Gal1, 4GlcNAc1- residue of sialylparagloboside and inhibit the binding of the A virus to erythrocytes which had been treated with sialidase and then reconstituted with sialylparagloboside. This antibody may be useful as an universal influenza vaccine effective to the wide variety of subtypes of influenza virus hemagglutinin.6) The strategy for the developing the universal influenza virus vaccine was discussed in relation to the anti-idiotypic antibody against the antibody directed to the influenza virus receptor, sialylparagloboside.7) A new common competitive inhibitor of influenza virus neuraminidase, ganglioside which contained thio-glycoside linkage between NeuAc and Gal was found. Less