a whole virus pandemic influenza h1n1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models整个大流行性流感病毒h1n1疫苗高免疫原性和保护主动免疫和被动保护小鼠模型.pdfVIP

A Whole Virus Pandemic Influenza H1N1 Vaccine Is Highly Immunogenic and Protective in Active Immunization and Passive Protection Mouse Models Otfried Kistner, Brian A. Crowe, Walter Wodal, Astrid Kerschbaum, Helga Savidis-Dacho, Nicolas Sabarth, Falko G. Falkner, Ines Mayerhofer, Wolfgang Mundt, Manfred Reiter, Leopold Grillberger, ¨ Christa Tauer, Michael Graninger, Alois Sachslehner, Michael Schwendinger, Peter Bruhl, Thomas R. Kreil, Hartmut J. Ehrlich, P. Noel Barrett* Global Research and Development, Baxter BioScience, Vienna, Austria Abstract The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus