title: New multi-determinant strategy for a group A streptococcal vaccine designed for the Australian Aboriginal population.
abstract: Infection with group A streptococci can result in acute and post-infectious pathology, including rheumatic fever and rheumatic heart disease. These diseases are associated with poverty and are increasing in incidence, particularly in developing countries and amongst indigenous populations, such as Australia's Aboriginal population, who suffer the highest incidence worldwide. Immunity to group A streptococci is mediated by antibodies against the M protein, a coiled-coil alpha helical surface protein of the bacterium. Vaccine development faces two substantial obstacles. Although opsonic antibodies directed against the N terminus of the protein are mostly responsible for serotypic immunity, more than 100 serotypes exist. Furthermore, whereas the pathogenesis of rheumatic fever is not well understood, increasing evidence indicates an autoimmune process. To develop a suitable vaccine candidate, we first identified a minimum, helical, non-host-cross-reactive peptide from the conserved C-terminal half of the protein and displayed this within a non-M-protein peptide sequence designed to maintain helical folding and antigenicity, J14 (refs. 8,9). As this region of the M protein is identical in only 70% of group A streptococci isolates, the optimal candidate might consist of the conserved determinant with common N-terminal sequences found in communities with endemic group A streptococci. We linked seven serotypic peptides with J14 using a new chemistry technique that enables the immunogen to display all the individual peptides pendant from an alkane backbone. This construct demonstrated excellent immunogenicity and protection in mice.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research, and The Australian Centre for International and Tropical Health and Nutrition, The University of Queensland, PO Royal Brisbane Hospital, Brisba, Australia.
authors.forename: E R
authors.initials: ER
authors.lastname: Brandt
authors.forename: K S
authors.initials: KS
authors.lastname: Sriprakash
authors.forename: R I
authors.initials: RI
authors.lastname: Hobb
authors.forename: W A
authors.initials: WA
authors.lastname: Hayman
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.forename: M R
authors.initials: MR
authors.lastname: Batzloff
authors.forename: D C
authors.initials: DC
authors.lastname: Jackson
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial; D001315:Australia / Q000453:epidemiology / Q000208:ethnology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology*; D001428:Bacterial Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015195:Drug Design; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013290:Streptococcal Infections / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013297:Streptococcus pyogenes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D018985:Epitopes, B-Lymphocyte; D010455:Peptides; D014614:Vaccines, Synthetic; C014689:streptococcal M protein