comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against h5n1 influenza in mouse and ferret比较血凝素的功效、核蛋白质和矩阵2蛋白质基于基因疫苗接种h5n1流感鼠标和雪貂.pdfVIP

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret 1 1 1 2 1 3 Srinivas S. Rao , Wing-Pui Kong , Chih-Jen Wei , Neal Van Hoeven , J. Patrick Gorres , Martha Nason , 4 2 1 Hanne Andersen , Terrence M. Tumpey , Gary J. Nabel * 1Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America, 2 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 3 Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America, 4 BIOQUAL, Inc., Rockville, Maryland, United States of America Abstract Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferret