title: Progress toward a universal H5N1 vaccine: a recombinant modified vaccinia virus Ankara-expressing trivalent hemagglutinin vaccine.
abstract: BACKGROUND
  The rapid evolution of new sublineages of H5N1 influenza poses the greatest challenge in control of H5N1 infection by currently existing vaccines. To overcome this, an MVAtor vector expressing three H5HA antigens A/Vietnam/1203/04, A/Indonesia/669/06 and A/Anhui/01/05 (MVAtor-tri-HA vector) was developed to elicit broad cross-protection against diverse clades by covering amino acid variations in the major neutralizing epitopes of HA among H5N1 subtypes.
  
  
  METHODS
  BALB/c mice and guinea pigs were immunized i.m. with 8×107 TCID50/animal of MVAtor-tri-HA vector. The immunogenicity and cross-protective immunity of the MVAtor-tri-HA vector was evaluated against diverse clades of H5N1 strains.
  
  
  RESULTS
  The results showed that mice immunized with MVAtor-tri-HA vector induced robust cross-neutralizing immunity to diverse H5N1 clades. In addition, the MVAtor-tri-HA vector completely protected against 10 MLD50 of a divergent clade of H5N1 infection (clade 7). Importantly, the serological surveillance of post-vaccinated guinea pig sera demonstrated that MVAtor-tri-HA vector was able to elicit strong cross-clade neutralizing immunity against twenty different H5N1 strains from six clades that emerged between 1997 and 2012.
  
  
  CONCLUSIONS
  The present findings revealed that incorporation of carefully selected HA genes from divergent H5N1 strains within a single vector could be an effective approach in developing a vaccine with broad coverage to prevent infection during a pandemic situation.
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
authors.forename: Mookkan
authors.initials: M
authors.lastname: Prabakaran
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Sonja
authors.initials: S
authors.lastname: Leyrer
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Auer
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
authors.forename: Subaschandrabose R
authors.initials: SR
authors.lastname: Kumar
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kindsmueller
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Nutan
authors.initials: N
authors.lastname: Mytle
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Emergent BioSolutions Inc., Rockville, Maryland, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lockhart
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kwang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002460:Cell Line; D056738:Cross Protection; D003429:Cross Reactions / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines