Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065.
Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10172-10177. doi: 10.1073/pnas.1707950114. Epub 2017 Sep 5.
The main barrier to reduction of morbidity caused by influenza is the absence of a vaccine that elicits broad protection against different virus strains. Studies in preclinical models of influenza virus infections have shown that antibodies alone are sufficient to provide broad protection against divergent virus strains in vivo. Here, we address the challenge of identifying an immunogen that can elicit potent, broadly protective, antiinfluenza antibodies by demonstrating that immune complexes composed of sialylated antihemagglutinin antibodies and seasonal inactivated flu vaccine (TIV) can elicit broadly protective antihemagglutinin antibodies. Further, we found that an Fc-modified, bispecific monoclonal antibody against conserved epitopes of the hemagglutinin can be combined with TIV to elicit broad protection, thus setting the stage for a universal influenza virus vaccine.
导致流感发病率的主要障碍是缺乏能够针对不同病毒株产生广泛保护的疫苗。流感病毒感染的临床前模型研究表明，单独的抗体足以在体内提供针对不同病毒株的广泛保护。在这里，我们通过证明由唾液酸化抗血凝素抗体和季节性灭活流感疫苗（TIV）组成的免疫复合物可以引发广泛保护性的抗血凝素抗体，来应对鉴定能够引发有效、广泛保护性的抗流感抗体的免疫原的挑战。此外，我们发现针对血凝素保守表位的 Fc 修饰双特异性单克隆抗体可以与 TIV 结合使用以引发广泛的保护，从而为通用流感病毒疫苗奠定了基础。
