Structural basis of influenza virus neutralization英文文献.pdfVIP

Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: The Year in Immunology Structural basis of influenza virus neutralization Thomas Han and Wayne A. Marasco Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts Address for correspondence: Wayne A. Marasco, M.D., Ph.D., Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 44 Binney Street, Boston, MA 02115. wayne_marasco@dfci.harvard.edu Although seasonal influenza vaccines play a valuable role in reducing the spread of virus at the population level, ongoing viral evolution to evade immune responses remains problematic. No current vaccines elicit enduring protec- tion in the face of emerging and re-emerging influenza viruses that are rapidly undergoing antigenic drift. Eliciting broadly cross-neutralizing antibody (nAb) responses against influenza virus is a crucial goal for seasonal and pan- demic influenza vaccine preparation. Recent three-dimensional structure information obtained from crystallization of influenza antigens in complex with nAbs has provided a framework for interpreting antibody-based viral neu- tralization that should aid in the design of vaccine immunogens. Here, we will review current knowledge of the structure-based mechanisms contributing to the neutralization and neutralization escape of influenza viruses. We will also explore the potential for this structure-based approach to overcome the obstacles in developing the highly desired “universal” influenza vaccine. Keywords: influenza; neutralizing antibodies; vaccine Influenza viruses are classified into three sub- Introduction types: A, B, an