Académie royale de Médecine de Belgique


Pierre Smeesters (ULB) - Résumé + vidéo

A vaccine against Streptococcus pyogenes at the horizon 2020 ?

par Pierre SMEESTERS (ULB).        

Streptococcus pyogenes or Group A Streptococcus (GAS) causes a massive disease burden that has been underestimated by global health authorities. It has been estimated that there are > 500,000 deaths annually due to the bacteria, mostly occurring in low and middle income countries. Disease caused by GAS ranges from superficial skin infection and pharyngitis to severe invasive disease and the post-streptococcal sequelae of acute rheumatic fever (ARF), rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis (PSGN). With no effective control strategies available for these diseases, a GAS vaccine is urgently needed.

Although there are no currently licensed GAS vaccines yet, the biological feasibility for GAS vaccine development is supported by several lines of evidence including the natural history of GAS, serologic data, animal and human challenge studies. GAS vaccine candidates can be broadly divided into M protein–based and non–M protein–based vaccines. The GAS has a broad armamentarium of virulence factors, but it is the M protein that is the major virulence determinant of the organism. The M protein is a coiled-coil protein consisting of three domains: an A repeat/N-terminal domain, which is highly variable and is used for epidemiologic molecular typing (emm typing); a B-repeat domain (antibodies against this region are not opsonic and some are cross-reactive with human tissues) and a conserved C-repeat domain. The two vaccines that have entered or are nearing clinical investigation are the N-terminal M protein-based multivalent vaccines (26-valent and 30-valent vaccines) and conserved M protein vaccines (the J8 vaccine and the StreptInCor vaccine). There are a variety of other vaccine candidates that are at various stages of discovery and development, some of them identified using reverse genomics.

The development of a global GAS vaccine has been hindered by the large diversity of circulating strains (emm-types) of GAS in low-incomes settings. Pioneering work in the 1950s showed that the presence of type specific antibodies are responsible for immunity against the homologous emm-type but does not confer protection against heterologous emm-type. Multivalent type specific vaccines would then offer high coverage in the USA and in Europe where only a few strains are predominant while the coverage in low-income settings would be lower due to the high diversity of circulating strains. Recent discoveries suggest however that antibodies against some emm-types may cross-protect against other emm-types. Confirmation of the cross protection hypothesis would represent an avenue for future GAS vaccine formulations.

The hopes for an efficient GAS vaccine at the horizon 2020 will be presented in the context of the recent international initiatives supporting its development.