具有临床应用价值的流感病毒广谱中和性抗体研究进展

Feasibility and importance of developing broadly neutralizing antibodies for clinical use against influenza viruses

流感病毒是RNA病毒,具有高度变异性。由于其高度的传染性和危害性,针对流感病毒的中和性抗体得到了广泛的研究。针对特定亚型的流感病毒,可以获得具备高度中和性、特异性和体内保护性的单克隆抗体,如中和H7N9禽流感病毒的单克隆抗体及中和H2N2亚型流感病毒的单克隆抗体。但是针对单一亚型流感病毒的单克隆抗体能够被流感病毒通过突变抗体结合表位附近的少量氨基酸甚至单个氨基酸而逃逸。通过免疫小鼠、噬菌体抗体库筛选或患者浆细胞筛选均可获得针对多种亚型流感病毒的广谱中和性抗体,但是针对不同亚型的流感病毒这些抗体的结合能力有较大差异,因此在临床应用中仍有较大难度。需要进一步采用新的方法提高针对各个流行亚型流感病毒的亲和力以开发具有临床应用价值的广谱中和性抗体。

Influenza virus is a RNA virus with high mutation rates. Because it is highly contagious and dangerous,neutralizing monoclonal antibodies against influenza viruses are widely studied. Highly neutralizing antibodies with high specificity and potency could be obtained for certain subtypes of influenza viruses,such as neutralizing antibodies against H7N9 avian flu virus and H2N2 influzenza virus. Broadly neutralizing antibodies against multiple subtypes of influenza viruses can be obtained by immunizing mice,screening phage display antibody libraries or screening plasma cells of patients. However,these antibodies are still far from clinical application because of their variable potency against different subtypes. More efforts need to be made to improve the affinity for different subtypes with newest methods to develop neutralizing antibodies that can be used clinically against prevalent subtypes of influenza viruses.