Current status of group A streptococcal vaccine development.

University of Tennessee Health Science Center, Memphis 38104, USA.
Advances in Experimental Medicine and Biology (Impact Factor: 2.01). 02/2008; 609:53-63. DOI: 10.1007/978-0-387-73960-1_5
Source: PubMed

ABSTRACT We now have a much more detailed understanding of the molecular pathogenesis of GAS infections. These discoveries have led to the identification of several vaccine candidates which are in various stages of development. One of the leading candidate antigens is the surface M protein, which confers protection against infection in animal models. In addition, M antibodies in human serum correlate with protection against infection with the homologous serotype of GAS. Molecular techniques have been used to genetically engineer highly complex multivalent M protein-based vaccines that appear to be free of potentially harmful tissue crossreactive epitopes. A 26-valent vaccine has been shown to be well-tolerated and immunogenic in adult volunteers and is now being considered for pediatric trials, which is the primary target group for the vaccine. Ongoing efforts are now addressing the epidemiology of GAS infections in developing countries so that new vaccines can be designed to prevent the infections that may trigger ARF and RHD. Successful deployment of safe and effective vaccines to prevent GAS infections and their complications could potentially have a significant impact on the health of millions of people around the world.

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    ABSTRACT: Background Group A streptococci (GAS) cause infections with a high prevalence in most developing countries. A GAS vaccine under trial that is based on the amino-terminus of the M protein provides type-specific immunity, and hence seems ineffective in India because of heterogeneous emm types. However, the conserved C-terminal region of the M protein protects against multiple serotypes. In this paper, the immune response generated against the conserved C-repeat region of the M protein was checked in an Indian population to establish their vaccine candidature. Methods When screened for GAS, patients with pharyngitis, rheumatic fever/rheumatic heart disease (RF/RHD), and invasive disease showed heterogeneous emm types, out of which five prevalent types (1-2, 11, 49, 75 and 112) were selected for the study. The C-terminal region of their M proteins showed conserved C1-, C2-, and C3-repeats. The C1-repeat was more diverse and had two different J14-like sequences. Peptides to these C-terminal regions (J14.1 and J14-R6) were designed. Antibodies against these peptides were analyzed using the sera of 130 GAS-infected volunteers. Results Serum antibodies were significantly higher in patients with acute rheumatic fever, RHD, and invasive disease than in patients with pharyngitis or the healthy controls. The serum antibodies to these peptides was higher in teenagers and adults than in children. Conclusion Results showed an association between streptococcal disease progression and the age-related development of immunity to the conserved regions. Hence, these peptides could be considered protective in impeding streptococcal infections worldwide.
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