Article

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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    • "This is in contrast to the influenza virus vaccine field where an antibody titer of 1:40, detected using the hemagglutination inhibition assay, is an accepted correlate of protection [9] [65]. These vaccine-induced correlates of protection are typically defined using multiple human vaccine studies [66] [67], which have not been performed for these M protein vaccines [18]. Future evaluation of the protective response in our model will focus on understanding the specific antibody:host interactions that can result in protection, even within a virus-weakened host. "
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    • "However because of the diversity of the M protein, this immunity can have limited coverage of strains. Current vaccine development initiatives are focussed either on multiple valency [6], or using conserved domain(s) in the M proteins do elicity proader immunity [7]. "
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    • "Previous studies indicate that opsonizing antibodies specific for M and M-like proteins of GAS are capable of providing protection against GAS infections [34]. Through antibody-induced complement activation followed by opsonization by C3b and its cleavage fragment iC3b, complement receptor 3 (CR3; CD11b/CD18) on phagocytes efficiently takes up and eliminates GAS [35]. "
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