title: Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers.
abstract: BACKGROUND
  Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome.
  
  
  METHODS
  The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies.
  
  
  RESULTS
  The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes.
  
  
  CONCLUSIONS
  On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.
authors.affiliation: Clinical Trials Research Center, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada. shelly.mcneil@cdha.nshealth.ca
authors.forename: Shelly A
authors.initials: SA
authors.lastname: McNeil
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.forename: Bruce
authors.initials: B
authors.lastname: Smith
authors.forename: Andrew
authors.initials: A
authors.lastname: Warren
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Sharratt
authors.forename: Darlene M
authors.initials: DM
authors.lastname: Baxendale
authors.forename: Mark A
authors.initials: MA
authors.lastname: Reddish
authors.forename: Mary C
authors.initials: MC
authors.lastname: Hu
authors.forename: Steven D
authors.initials: SD
authors.lastname: Stroop
authors.forename: Janine
authors.initials: J
authors.lastname: Linden
authors.forename: Louis F
authors.initials: LF
authors.lastname: Fries
authors.forename: Peter E
authors.initials: PE
authors.lastname: Vink
authors.forename: James B
authors.initials: JB
authors.lastname: Dale
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; C014689:streptococcal M protein; C119204:streptococcal protective antigen