title: Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor.
abstract: Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA(0) precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA(0) vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA(0), the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA(0) conjugate is not as efficacious as for influenza B virus.
authors.affiliation: Department of Molecular & Cell Biology, IRBM P. Angeletti, Via Pontina Km 30.600, 00040 Pomezia (Rome) Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Paolo
authors.initials: P
authors.lastname: Ingallinella
authors.forename: Marco
authors.initials: M
authors.lastname: Finotto
authors.forename: Michael A
authors.initials: MA
authors.lastname: Chastain
authors.forename: Jiang
authors.initials: J
authors.lastname: Fan
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Hong Chang
authors.initials: HC
authors.lastname: Song
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Horton
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.forename: Walter
authors.initials: W
authors.lastname: Manger
authors.forename: Emily
authors.initials: E
authors.lastname: Wen
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.forename: Roxana
authors.initials: R
authors.lastname: Ionescu
authors.forename: Colleen
authors.initials: C
authors.lastname: Price
authors.forename: Marc
authors.initials: M
authors.lastname: Wenger
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: Antonello
authors.initials: A
authors.lastname: Pessi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015195:Drug Design; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D010455:Peptides; D011498:Protein Precursors; D018074:Vaccines, Conjugate