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The overall goal of this project is to develop a safe and effective vaccine that would prevent group A streptococcal infection.
Previous studies have shown that M proteins, the major protective antigens of these organisms, contain both protective as well as potentially harmful tissue- crossreactive epitopes. The previous funding period focused on the identification of protective epitopes of 'rheumatogenic' M proteins and their separation from the potentially harmful autoimmune epitopes.
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The Specific Aims for this renewal proposal are: <ol> <li>To determine the primary structures of defined regions of selected serotypes of M proteins that contain protective as opposed to tissue-crossreactive epitopes.
<li>To construct recombinant, multivalent M protein vaccines and to determine protein conformations that evoke optimal protective immune responses in laboratory animals.
<li>To determine indirectly the potential protective efficacy of multivalent M protein vaccines.
<li>To develop strategies of mucosal delivery of multivalent M proteins that evoke local and systemic protective immune response.
<li>To determine the minimal primary structures of selected M proteins that are capable of activating bactericidal T lymphocytes in vitro.</ol>