title: Evaluation of synthetic, M type-specific peptides as antigens in a multivalent group A streptococcal vaccine.
abstract: The recent development of emm gene sequence-based typing methodology has allowed group A streptococci (GAS) M serotype prevalence data to be determined. This information has been used to identify the components of a multivalent M protein peptide vaccine that could theoretically prevent most of the GAS-mediated diseases in the USA. In this study, we have evaluated in mice the immunogenicity and protective ability of multiple synthetic, M type-specific peptides, derived from the N-termini of three prevalent GAS serotypes (three peptides per serotype, total of nine peptides). At least one peptide, representing each of the three M types tested, was immunogenic. Five of the nine synthetic peptides tested, elicited an immune response in mice, and sera raised against four of the peptides, all possessed functional activity as demonstrated in a bactericidal assay. In vivo nasopharyngeal challenge experiments were carried out with peptides from the M1 (peptide M1-3) and M3 (peptide M3-2) proteins induced in vivo immune protection by reducing intranasal carriage. Reduction in colonization for M1-3 and M3-2 was 90% (P=0.02) and 66% (P<0.17), respectively. A reduction in colonization of 67% (P=0.03) was observed for M3-2 immunized mice when M43, a heterologous serotype, was used as the challenge strain. These results show the utility of synthetic, M type-specific peptides as antigens in a multivalent GAS vaccine.
authors.affiliation: Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G05, Atlanta, GA 30333, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bruner
authors.forename: A
authors.initials: A
authors.lastname: James
authors.forename: B
authors.initials: B
authors.lastname: Beall
authors.forename: G M
authors.initials: GM
authors.lastname: Carlone
authors.forename: E
authors.initials: E
authors.lastname: Ades
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Guarner
authors.forename: J
authors.initials: J
authors.lastname: Sampson
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D007279:Injections, Subcutaneous; D051379:Mice; D009305:Nasopharynx / Q000382:microbiology; D010455:Peptides / Q000276:immunology*; D011817:Rabbits; D012703:Serotyping; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D010455:Peptides; D022541:Streptococcal Vaccines; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; C014689:streptococcal M protein