title: Protective and nonprotective epitopes from amino termini of M proteins from Australian aboriginal isolates and reference strains of group A streptococci.
abstract: The M protein is the primary vaccine candidate to prevent group A streptococcal (GAS) infection and the subsequent development of rheumatic fever (RF). However, the large number of serotypes have made it difficult to design a vaccine against all strains. We have taken an approach of identifying amino-terminal M protein epitopes from GAS isolates that are highly prevalent in GAS-endemic populations within the Northern Territory (NT) of Australia. Australian Aboriginals in the NT experience the highest incidence of RF worldwide. To develop a vaccine for this population, 39 peptides were synthesized, representing the amino-terminal region of the M protein from endemic GAS. Mice immunized with these peptides covalently linked to tetanus toxoid and emulsified in complete Freund's adjuvant raised high-titer antibodies. Over half of these sera reduced bacterial colony counts by >80% against the homologous isolate of GAS. Seven of the peptide antisera also cross-reacted with at least three other heterologous peptides by enzyme-linked immunosorbent assay. Antiserum to one peptide, BSA10(1-28), could recognize six other peptides, and five of these peptides could inhibit opsonization mediated by BSA10(1-28) antiserum. Cross-opsonization studies showed that six of these sera could opsonize at least one heterologous isolate of GAS. These data reveal vaccine candidates specific to a GAS-endemic area and show the potential of some to cross-opsonize multiple isolates of GAS. This information will be critical when considering which epitopes may be useful in a multiepitope vaccine to prevent GAS infection.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, and the Australian Centre for International and Tropical Health and Nutrition, University of Queensland, PO Royal Brisbane Hospital, Queensland, Australia.
authors.forename: E R
authors.initials: ER
authors.lastname: Brandt
authors.forename: T
authors.initials: T
authors.lastname: Teh
authors.forename: W A
authors.initials: WA
authors.lastname: Relf
authors.forename: R I
authors.initials: RI
authors.lastname: Hobb
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007106:Immune Sera; D010446:Peptide Fragments; D022541:Streptococcal Vaccines; C014689:streptococcal M protein