Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers

Clin Infect Dis. 2005 Oct 15;41(8):1114-22. doi: 10.1086/444458. Epub 2005 Sep 12.


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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / immunology
  • Carrier Proteins / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / immunology
  • Streptococcal Infections / prevention & control*
  • Streptococcal Vaccines / immunology*
  • Streptococcus pyogenes / immunology
  • Vaccines, Synthetic / immunology


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Recombinant Fusion Proteins
  • Streptococcal Vaccines
  • Vaccines, Synthetic
  • streptococcal M protein
  • streptococcal protective antigen