title: Transient humoral protection against H5N1 challenge after seasonal influenza vaccination of humans.
abstract: Current influenza vaccines are believed to confer protection against a narrow range of virus strains. The identification of broadly influenza neutralizing antibodies (bnAbs) has triggered efforts to develop vaccines providing 'universal' protection against influenza. Several bnAbs were isolated from humans recently vaccinated with conventional influenza vaccines, suggesting that such vaccines could, in principle, be broadly protective. Assessing the breadth-of-protection conferred to humans by influenza vaccines is hampered by the lack of in vitro correlates for broad protection. We designed and employed a novel human-to-mouse serum transfer and challenge model to analyze protective responses in serum samples from clinical trial subjects. One dose of seasonal vaccine induces humoral protection not only against vaccine-homologous H1N1 challenge, but also against H5N1 challenge. This heterosubtypic protection is neither detected, nor accurately predicted by in vitro immunogenicity assays. Moreover, heterosubtypic protection is transient and not boosted by repeated inoculations. Strategies to increase the breadth and duration of the protective response against influenza are required to obtain 'universal' protection against influenza by vaccination. In the absence of known correlates of protection for broadly protective vaccines, the human-to-mouse serum transfer and challenge model described here may aid the development of such vaccines.
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Ramon
authors: R
authors: Roozendaal
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Jeroen
authors: J
authors: Tolboom
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Anna
authors: A
authors: Roos
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Sarra
authors: S
authors: Riahi
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Jessica
authors: J
authors: Theeuwsen
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Miriam V
authors: MV
authors: Bujny
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Vincent
authors: V
authors: Klaren
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Hans J W M
authors: HJ
authors: Korse
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Liesbeth
authors: L
authors: Dekking
authors: Clinical Immunology, Crucell Holland BV, Leiden, the Netherlands.
authors: Arijan
authors: A
authors: Grootenhuis
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Gerrit Jan
authors: GJ
authors: Weverling
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Wouter
authors: W
authors: Koudstaal
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Jaap
authors: J
authors: Goudsmit
authors: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Crucell Holland BV, Leiden, the Netherlands.
authors: Katarina
authors: K
authors: Radošević
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D019540:Area Under Curve; D045744:Cell Line, Tumor; D056738:Cross Protection; D004285:Dogs; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D012372:ROC Curve; D012621:Seasons; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D007252:Influenza Vaccines