Group A streptococcal vaccines: facts versus fantasy

Abstract

This review provides an overview of progress of the development of group A streptococcal (GAS) vaccines with a focus on recent advances. Historically, GAS vaccine development has focused on the N-terminus of the M protein, which ultimately led to successful phase I/II clinical trials of a 26-valent recombinant M protein vaccine in 2004–2005. More recently, interest in antigens conserved among most, if not all, group A streptococci has increased. However, no vaccines containing these antigens have reached clinical trials. Three strategies have been used to develop conserved antigen vaccine candidates: use of the conserved region of the M protein; use of well described virulence factors as antigens, including streptococcal C5a peptidase, streptococcal carbohydrate, fibronectin-binding proteins, cysteine protease and streptococcal pili; and use of reverse vaccinology to identify novel antigens. Several vaccine candidates against GAS infection are in varying stages of preclinical and clinical development. Although there is great hope that one of these vaccine candidates will reach licensure in the next decade, only one, the multivalent N-terminal vaccine, has entered clinical trials in the last 30 years. Although strong advocacy for GAS vaccine development is important, there remains an urgent need to institute available public health control measures against GAS diseases globally, particularly in developing countries.