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While for decades the development of a vaccine has been the center of attention in many laboratories worldwide, with some successes, no corporate development has yet to be initiated. The reason for this probably lies in our inability to conclusively identify the streptococcal molecule or molecules responsible for the heart cross-reactive antibodies observed in the serum of rheumatic fever patients. Without this specific knowledge, any streptococcal vaccine antigen is suspect and thus not the target for a billion-dollar investment, despite the fact that the exact role of cross-reactive antibodies in rheumatic fever is still questionable. This article will describe the development of several approaches to protect against<jats:italic>Streptococcus pyogenes<\/jats:italic>infections over the past several decades.<\/jats:p>","DOI":"10.1128\/microbiolspec.gpp3-0010-2018","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T12:48:13Z","timestamp":1558442893000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Vaccine Approaches To Protect against Group A Streptococcal Pharyngitis"],"prefix":"10.1128","volume":"7","author":[{"given":"Vincent A.","family":"Fischetti","sequence":"first","affiliation":[{"name":"The Rockefeller University, New York, NY 10065"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"crossref","unstructured":"Stevens DL. 1992. Invasive group A streptococcus infections. Clin Infect Dis 14: 2\u201311 http:\/\/dx.doi.org\/10.1093\/clinids\/14.1.2. [PubMed]","key":"e_1_3_1_2_2","DOI":"10.1093\/clinids\/14.1.2"},{"doi-asserted-by":"crossref","unstructured":"Carapetis JR Steer AC Mulholland EK Weber M. 2005. The global burden of group A streptococcal diseases. Lancet Infect Dis 5: 685\u2013694 http:\/\/dx.doi.org\/10.1016\/S1473-3099(05)70267-X.","key":"e_1_3_1_3_2","DOI":"10.1016\/S1473-3099(05)70267-X"},{"doi-asserted-by":"crossref","unstructured":"Veasy LG Wiedmeier SE Orsmond GS Ruttenberg HD Boucek MM Roth SJ Tait VF Thompson JA Daly JA Kaplan EL Hill HR. 1987. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 316: 421\u2013427 http:\/\/dx.doi.org\/10.1056\/NEJM198702193160801. [PubMed]","key":"e_1_3_1_4_2","DOI":"10.1056\/NEJM198702193160801"},{"unstructured":"Dodu SRA B\u00f6thig S. 1989. Rheumatic fever and rheumatic heart disease in developing countries. 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