title: Group A streptococcal vaccines: paving a path for accelerated development.
abstract: Group A streptococci (GAS) are important causes of morbidity and mortality worldwide. These organisms cause a wide spectrum of disease, ranging from uncomplicated sore throat to invasive, life-threatening infections, as well as immune complications such as acute rheumatic fever (ARF), rheumatic heart disease (RHD) and acute post-streptococcal glomerulonephritis (APSGN). Vaccine prevention of GAS infections and their immunological complications has been a goal of researchers for decades. Several vaccine candidates against GAS infection are in various stages of pre-clinical and clinical development, including M protein-based vaccines (N-terminal vaccine candidates and M protein conserved region vaccines), and non-M protein vaccine candidates representing conserved GAS antigens. Some of the obstacles to GAS vaccine development are related to the complexity of the global epidemiology of GAS infections, the limitation in the criteria for selection of antigens to include in combination vaccines as well as the issues around autoimmunity and vaccine safety, among others. Overcoming these obstacles will require collaborative efforts to develop innovative strategies that address key steps in the pre-clinical and clinical development process, as well as clearly defining the global burden of GAS diseases and the molecular epidemiology of infections. Specific recommendations are presented for an accelerated plan leading to the introduction of a broadly protective vaccine designed for deployment in low-, middle-, and high-income countries.
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN 38163, USA. jbdale@uthsc.edu
authors.forename: James B
authors.initials: JB
authors.lastname: Dale
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Carapetis
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Steer
authors.forename: Samba
authors.initials: S
authors.lastname: Sow
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
authors.forename: Fran A
authors.initials: FA
authors.lastname: Rubin
authors.forename: Kim
authors.initials: K
authors.lastname: Mulholland
authors.forename: Joachim Maria
authors.initials: JM
authors.lastname: Hombach
authors.forename: Florian
authors.initials: F
authors.lastname: Schödel
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Henao-Restrepo
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D035843:Biomedical Research / Q000639:trends*; D002352:Carrier Proteins / Q000276:immunology; D017281:Cost of Illness; D006801:Humans; D017720:Molecular Epidemiology; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000627:therapeutic use*; D013297:Streptococcus pyogenes
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D022541:Streptococcal Vaccines; C014689:streptococcal M protein