title: Protection against H5N1 by multiple immunizations with seasonal influenza vaccine in mice is correlated with H5 cross-reactive antibodies.
abstract: BACKGROUND
  Current seasonal influenza vaccines are believed to confer protection against a narrow range of virus strains. However, their protective ability is commonly estimated based on an in vitro correlate of protection that only considers a subset of anti-influenza antibodies that are typically strain specific, i.e., hemagglutination inhibiting antibodies. Here, we evaluate the breadth of protection induced with a seasonal trivalent influenza vaccine (composition H1N1 A/California/07/09, H3N2 A/Victoria/210/08, B/Brisbane/60/08) against influenza challenge in mice.
  
  
  METHODS
  Balb/c mice were immunized once, twice, or three times with seasonal influenza vaccine to assess protection against heterosubtypic H5N1 influenza challenge, or homologous H1N1 influenza virus as a control. Passive transfer of immune serum was used to determine the contribution of humoral immunity to protection.
  
  
  RESULTS
  Multiple immunizations with seasonal influenza vaccine induced up to 80% protection against heterosubtypic H5N1 influenza challenge in mice without eliciting detectable H5N1 neutralizing antibodies. Comparable levels of protection were reached by passive transfer of immune serum, and protection was correlated with the titer of vaccine-induced, H5 cross-reactive, non-neutralizing antibodies that are at least in part directed against conserved HA epitopes.
  
  
  CONCLUSIONS
  Here, we demonstrate that seasonal vaccine has the ability to induce broad serum-mediated protection, and that the mechanism of this protection is different from the vaccine-induced homologous protection.
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Anna
authors: A
authors: Roos
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands. Electronic address: RRoozend@its.jnj.com.
authors: Ramon
authors: R
authors: Roozendaal
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Jessica
authors: J
authors: Theeuwsen
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Sarra
authors: S
authors: Riahi
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Joost
authors: J
authors: Vaneman
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Jeroen
authors: J
authors: Tolboom
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Infectious Diseases and Vaccines Therapeutic area, Janssen Research and Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Liesbeth
authors: L
authors: Dekking
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Janssen Prevention Center, Center of Excellence within Janssen Research & Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Wouter
authors: W
authors: Koudstaal
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Janssen Prevention Center, Center of Excellence within Janssen Research & Development, A Division of Janssen Pharmaceutica, Leiden, The Netherlands.
authors: Jaap
authors: J
authors: Goudsmit
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland B.V., Leiden, The Netherlands; Sanofi, Global Biotherapeutics, Vitry-sur-Seine, France.
authors: Katarina
authors: K
authors: Radošević
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology*; D012621:Seasons
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: Correlate of protection.; Heterosubtypic protection; Influenza challenge model; Mice; Seasonal influenza vaccine; Serum transfer