Prevention And Control

Vaccines for ยก-Haemolytic Streptococcal Disease

GAS opsonic antibodies directed against the N-terminal sequences of the streptococcal M protein are known to confer strain-specific immunity to S. pyogenes. There is therefore an obvious advantage to exploiting the M protein as a vaccine candidate. Unfortunately, there are in excess of 100 M serotypes and in excess of 150 emm gene types, impeding the process of choosing vaccine candidates. Indeed, the prevalent M serotypes in different communities differ significantly. To counter this multivalent vaccines have been designed that incorporate several dominant M serotypes. A recombinant multivalent vaccine has recently undergone phase I clinical trial evaluation

(Kotloff etal. 2004), which has provided the first evidence that a hybrid fusion protein is a feasible strategy for evoking type-specific opsonic antibodies against multiple serotypes of GAS without eliciting antibodies that cross-react with host tissues. This represents a critical step in GAS vaccine development.

The conserved C-terminus of the M protein has also been considered as a vaccine candidate. Conserved T-cell epitopes, which are thought to be rheumatogenic, reside in the C-terminus of the protein (Robinson, Case and Kehoe 1993; Pruksakorn etal. 1994), though rheumatogenic T-cell epitopes may also exist in the variable N-terminus (Guilherme etal. 2000). These considerations have greatly complicated GAS vaccine development because of fears of precipitating RF in vaccinated individuals (Pruksakorn etal. 1994; Brandt etal. 2000).

Recent studies suggest that opsonic antibodies to M protein alone are insufficient for opsonophagocytosis of S. pyogenes, emphasising the need to seek additional vaccine candidates. Certain non-M-protein antigens have already been evaluated in preclinical models, including the streptococcal C5a peptidase, the streptococcal cysteine protease (SPEB) and the GAS carbohydrate.

Although maternal intrapartum antibiotic prophylaxis is clearly effective and has reduced the incidence of early-onset GBS neonatal disease substantially in the United States, it cannot prevent late-onset GBS disease. Vaccination of women of childbearing age against GBS could theoretically prevent both early-onset and late-onset GBS disease in the neonate, in addition to preventing GBS disease in pregnant women. Opsonic antibodies directed against the capsular polysaccharide of GBS confer serotype-specific protection. Initial vaccines developed focused on capsular type III isolates, but the emergence of type V isolates in recent years has prompted the development of a polyvalent GBS vaccine (Baker and Edwards 2003). Vaccines have been developed by coupling purified capsular polysaccharide antigen of GBS with an immunogenic protein carrier. Glycoconjugate vaccines against all nine currently identified GBS serotypes have been synthesised and shown to be immunogenic in animal models and in human phase I and II trials. The recent results strongly suggest that GBS conjugate vaccines may be effective in the prevention of GBS disease (Paoletti and Kasper 2003).

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