{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:30:01Z","timestamp":1793320201146,"version":"4.5.0"},"reference-count":193,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1132975"],"award-info":[{"award-number":["1132975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.<\/jats:p>","DOI":"10.3390\/vaccines7030058","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T10:54:47Z","timestamp":1561978487000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems against Group A Streptococcus"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5140-4297","authenticated-orcid":false,"given":"Armira","family":"Azuar","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-586X","authenticated-orcid":false,"given":"Wanli","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Mukaida","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed M.","family":"Hussein","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Toth","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"School of Pharmacy, Woolloongabba, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"Institute of Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-807X","authenticated-orcid":false,"given":"Mariusz","family":"Skwarczynski","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nrmicro2648","article-title":"Molecular insight into invasive Group A Streptococcal disease","volume":"9","author":"Cole","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","article-title":"The global burden of Group A Streptococcal diseases","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","unstructured":"Hill, D.R., Solomon, T., and Ryan, E.T. (2013). Group A Streptococcus In Hunter\u2019s Tropical Medicine and Emerging Infectious Disease, W.B. Saunders. [9th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5448","DOI":"10.4049\/jimmunol.175.8.5448","article-title":"T cell mimicry and epitope specificity of cross-reactive T cell clones from rheumatic heart disease","volume":"175","author":"Ellis","year":"2005","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/CMR.13.3.470","article-title":"Pathogenesis of Group A Streptococcal infections","volume":"13","author":"Cunningham","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Root-Bernstein, R. (2014). Rethinking molecular mimicry in rheumatic heart disease and autoimmune myocarditis: Laminin, collagen IV, CAR, and B1AR as initial targets of disease. Front. Pediatr., 2.","DOI":"10.3389\/fped.2014.00085"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18686","DOI":"10.1074\/jbc.M701047200","article-title":"Identification of a streptococcal octapeptide motif involved in acute rheumatic fever","volume":"282","author":"Dinkla","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1172\/JCI17247","article-title":"Rheumatic fever-associated Streptococcus pyogenes isolates aggregate collagen","volume":"111","author":"Dinkla","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Giese, M. (2013). Development of subunit vaccines for Group A Streptococcus. Molecular Vaccines: From Prophylaxis to Therapy\u2014Volume 1, Springer.","DOI":"10.1007\/978-3-7091-1419-3"},{"key":"ref_10","unstructured":"Plotkin, S.A., Orenstein, W.A., and Offit, P.A. (2013). Streptococcus Group A vaccines. Vaccines, W.B. Saunders. [6th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/scientificamerican0691-58","article-title":"Streptococcal M protein","volume":"264","author":"Fischetti","year":"1991","journal-title":"Sci. Am."},{"key":"ref_12","unstructured":"World Health Organization (2005). The Current Evidence for the Burden of Group A Streptococcal Diseases, WHO."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1172\/JCI38095","article-title":"A decade of molecular pathogenomic analysis of Group A Streptococcus","volume":"119","author":"Musser","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1056\/NEJMoa1603693","article-title":"Global, regional, and national burden of rheumatic heart disease, 1990\u20132015","volume":"377","author":"Watkins","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/j.amjcard.2010.01.364","article-title":"Prevalence of rheumatic heart disease in children and young adults in Nicaragua","volume":"105","author":"Paar","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"ref_16","unstructured":"Ferretti, J.J., Stevens, D.L., and Fischetti, V.A. (2016). Global disease burden of Group A Streptococcus. Streptococcus pyogenes: Basic Biology to Clinical Manifestations, University of Oklahoma Health Sciences Center."},{"key":"ref_17","unstructured":"Ferretti, J.J., Stevens, D.L., and Fischetti, V.A. (2016). Epidemiology of Streptococcus pyogenes. Streptococcus pyogenes: Basic Biology to Clinical Manifestations, University of Oklahoma Health Sciences Center."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1093\/clinids\/14.1.2","article-title":"Invasive Group A Streptococcus infections","volume":"14","author":"Stevens","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1046\/j.1469-0691.2003.00493.x","article-title":"Predominance of two M-types among erythromycin-resistant Group A Streptococci from Greek children","volume":"9","author":"Zachariadou","year":"2003","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3201\/eid0204.960410","article-title":"Rapid increase of resistance to erythromycin and clindamycin in Streptococcus pyogenes in Italy, 1993\u20131995. The Italian surveillance group for antimicrobial resistance","volume":"2","author":"Cornaglia","year":"1996","journal-title":"Emerg. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1128\/JCM.42.12.5620-5623.2004","article-title":"Prevalence and mechanisms of erythromycin resistance in Group A and Group B Streptococcus: Implications for reporting susceptibility results","volume":"42","author":"Desjardins","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_22","unstructured":"World Health Organization (2005). Group A Streptococcal Vaccine Development: Current Status and Issues of Relevance to Less Developed Countries, WHO."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20130433","DOI":"10.1098\/rstb.2013.0433","article-title":"The contribution of vaccination to global health: Past, present and future","volume":"369","author":"Greenwood","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1073\/pnas.1400472111","article-title":"History of vaccination","volume":"111","author":"Plotkin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","unstructured":"Koutsopoulos, S. (2018). Peptide-based vaccines. Peptide Applications in Biomedicine, Biotechnology and Bioengineering, Woodhead Publishing."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1039\/C5SC03892H","article-title":"Peptide-based synthetic vaccines","volume":"7","author":"Skwarczynski","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"778","DOI":"10.4161\/hv.27332","article-title":"Recent progress in adjuvant discovery for peptide-based subunit vaccines","volume":"10","author":"Azmi","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_29","unstructured":"Kastin, A. (2013). Lipo-peptides\/saccharides for peptide vaccine delivery. Handbook of the Biologically Active Peptides, Elsevier Inc.. [2nd ed.]."},{"key":"ref_30","unstructured":"Ferretti, J.J., Stevens, D.L., and Fischetti, V.A. (2016). Current approaches to Group A Streptococcal vaccine development. Streptococcus pyogenes: Basic Biology to Clinical Manifestations, University of Oklahoma Health Sciences Center."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1586\/14760584.2015.1081817","article-title":"Strategic development of the conserved region of the M protein and other candidates as vaccines to prevent infection with Group A Streptococci","volume":"14","author":"Good","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5835","DOI":"10.1016\/j.vaccine.2008.08.037","article-title":"Genetic diversity of Group A Streptococcus m protein: Implications for typing and vaccine development","volume":"26","author":"Smeesters","year":"2008","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/j.vaccine.2011.12.115","article-title":"Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein","volume":"30","author":"Bauer","year":"2012","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"B216","DOI":"10.1016\/j.vaccine.2012.09.045","article-title":"Group A Streptococcal vaccines: Paving a path for accelerated development","volume":"31","author":"Dale","year":"2013","journal-title":"Vaccine"},{"key":"ref_35","first-page":"709","article-title":"Failure of type specific Streptococcus pyogenes vaccine to prevent respiratory infections","volume":"46","author":"Young","year":"1946","journal-title":"U.S. Navy Med. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1128\/am.16.3.509-518.1968","article-title":"Secondary and apparent primary antibody responses after Group A Streptococcal vaccination of 21 children","volume":"16","author":"Massell","year":"1968","journal-title":"Appl. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1001\/jama.1969.03150190037007","article-title":"Rheumatic fever following Streptococcal vaccination: Report of three cases","volume":"207","author":"Massell","year":"1969","journal-title":"J. Am. Med. Assoc."},{"key":"ref_38","unstructured":"Food and Drug Administration (2005). Revocation of status of specific products; Group A streptococcus. Direct final rule. Fed. Regist., 70, 72197\u201372199."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1084\/jem.124.6.1135","article-title":"Antigenicity of the M proteins of group A hemolytic streptococci. III. Antibody responses and cutaneous hypersensitivity in humans","volume":"124","author":"Fox","year":"1966","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/infdis\/120.5.598","article-title":"Primary immunization of infants and children with Group A Streptococcal M protein","volume":"120","author":"Fox","year":"1969","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1172\/JCI107372","article-title":"Protective study with a Group A Streptococcal M protein vaccine. Infectivity challenge of human volunteers","volume":"52","author":"Fox","year":"1973","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/infdis\/131.3.217","article-title":"Protective studies with a Group A Streptococcal M Protein Vaccine. II. Challenge of volunteers after local immunization in the upper respiratory tract","volume":"131","author":"Polly","year":"1975","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.4049\/jimmunol.143.8.2677","article-title":"Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence Gln-Lys-Ser-Lys-Gln in M protein","volume":"143","author":"Cunningham","year":"1989","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1084\/jem.161.1.113","article-title":"Multiple, heart-cross-reactive epitopes of streptococcal M proteins","volume":"161","author":"Dale","year":"1985","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1084\/jem.164.5.1785","article-title":"Sequence of myosin-crossreactive epitopes of streptococcal M protein","volume":"164","author":"Dale","year":"1986","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1084\/jem.167.6.1849","article-title":"Protective and heart-crossreactive epitopes located within the NH2 terminus of type 19 streptococcal M protein","volume":"167","author":"Bronze","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/intimm\/6.8.1235","article-title":"Identification of T cell autoepitopes that cross-react with the C-terminal segment of the M protein of Group A Streptococci","volume":"6","author":"Pruksakorn","year":"1994","journal-title":"Int. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1128\/iai.65.9.3913-3923.1997","article-title":"Molecular analysis of human cardiac myosin-cross-reactive B- and T-cell epitopes of the Group A Streptococcal M5 protein","volume":"65","author":"Cunningham","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1093\/intimm\/9.11.1723","article-title":"Mapping the minimal murine T cell and B cell epitopes within a peptide vaccine candidate from the conserved region of the M protein of Group A Streptococcus","volume":"9","author":"Hayman","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1128\/IAI.66.9.4418-4424.1998","article-title":"Immunological relationship between the class I epitope of streptococcal M protein and myosin","volume":"66","author":"Quinn","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.tim.2010.02.007","article-title":"The streptococcal m protein: A highly versatile molecule","volume":"18","author":"Smeesters","year":"2010","journal-title":"Trend Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1086\/504266","article-title":"Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against Group A Streptococcus","volume":"193","author":"Olive","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/IAI.71.5.2373-2383.2003","article-title":"Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens","volume":"71","author":"Olive","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.vaccine.2004.01.043","article-title":"Identification and assessment of new vaccine candidates for Group A Streptococcal infections","volume":"22","author":"McMillan","year":"2004","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1097\/QCO.0b013e328332bbfe","article-title":"Group A Streptococcal vaccines: Facts versus fantasy","volume":"22","author":"Steer","year":"2009","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/QCO.0b013e3283458f7e","article-title":"New understandings in Streptococcus pyogenes","volume":"24","author":"Lynskey","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_57","first-page":"121","article-title":"Prospecting for new Group A Streptococcal vaccine candidates","volume":"119 Suppl","author":"McMillan","year":"2004","journal-title":"Indian J. Med. Res."},{"key":"ref_58","first-page":"e00618","article-title":"Differing efficacies of lead Group A Streptococcal vaccine candidates and full-length m protein in cutaneous and invasive disease models","volume":"7","author":"Pandey","year":"2016","journal-title":"mBio"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s00109-012-0897-9","article-title":"Conserved anchorless surface proteins as Group A Streptococcal vaccine candidates","volume":"90","author":"Henningham","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1099\/jmm.0.46224-0","article-title":"Characterization of Group A Streptococci (Streptococcus pyogenes): Correlation of m-protein and emm-gene type with T-protein agglutination pattern and serum opacity factor","volume":"55","author":"Johnson","year":"2006","journal-title":"J. Med. Microbiol."},{"key":"ref_61","unstructured":"Ferretti, J.J., Stevens, D.L., and Fischetti, V.A. (2016). M protein and other surface proteins on Streptococci. Streptococcus pyogenes: Basic Biology to Clinical Manifestations, University of Oklahoma Health Sciences Center."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.2174\/092986707782794069","article-title":"Towards the development of a broadly protective Group A Streptococcal vaccine based on the lipid-core peptide system","volume":"14","author":"Olive","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Beres, S.B., and Musser, J.M. (2007). Contribution of exogenous genetic elements to the Group A Streptococcus metagenome. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000800"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/j.vaccine.2006.11.031","article-title":"Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein\/SfbI lipid core peptide vaccine formulation","volume":"25","author":"Olive","year":"2007","journal-title":"Vaccine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0161-5890(97)00056-4","article-title":"Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins","volume":"34","author":"Cooper","year":"1997","journal-title":"Mol. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1016\/S0264-410X(03)00165-8","article-title":"Evaluation of synthetic, M type-specific peptides as antigens in a multivalent Group A Streptococcal vaccine","volume":"21","author":"Bruner","year":"2003","journal-title":"Vaccine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1128\/IAI.70.4.2171-2177.2002","article-title":"Immunogenicity of a 26-valent Group A Streptococcal vaccine","volume":"70","author":"Hu","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8175","DOI":"10.1016\/j.vaccine.2011.09.005","article-title":"New 30-valent M protein-based vaccine evokes cross-opsonic antibodies against non-vaccine serotypes of Group A Streptococci","volume":"29","author":"Dale","year":"2011","journal-title":"Vaccine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1086\/426443","article-title":"High diversity of Group A Streptococcal emm types in an Indian community: The need to tailor multivalent vaccines","volume":"40","author":"Dey","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0264-410X(98)00150-9","article-title":"Multivalent Group A Streptococcal vaccine designed to optimize the immunogenicity of six tandem M protein fragments","volume":"17","author":"Dale","year":"1999","journal-title":"Vaccine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/jama.292.6.709","article-title":"Safety and immunogenicity of a recombinant multivalent Group A Streptococcal vaccine in healthy adults: Phase 1 trial","volume":"292","author":"Kotloff","year":"2004","journal-title":"J. Am. Med. Assoc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1086\/444458","article-title":"Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers","volume":"41","author":"McNeil","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ics.2005.12.002","article-title":"A double-blind, randomized Phase II trial of the safety and immunogenicity of 26-valent Group A Streptococcus vaccine in healthy adults","volume":"1289","author":"McNeil","year":"2006","journal-title":"Int. Congr. Ser."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.vaccine.2013.01.019","article-title":"Potential coverage of a multivalent M protein-based Group A Streptococcal vaccine","volume":"31","author":"Dale","year":"2013","journal-title":"Vaccine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.vaccine.2016.11.065","article-title":"Structure-based design of broadly protective Group A Streptococcal M protein-based vaccines","volume":"35","author":"Dale","year":"2017","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1086\/521264","article-title":"The epidemiology of invasive Group A Streptococcal infection and potential vaccine implications: United States, 2000\u20132004","volume":"45","author":"Roberson","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1086\/599344","article-title":"Seven-year surveillance of north american pediatric Group A Streptococcal pharyngitis isolates","volume":"49","author":"Shulman","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1128\/JCM.02155-08","article-title":"Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe","volume":"47","author":"Darenberg","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1016\/j.vaccine.2016.03.073","article-title":"Status of research and development of vaccines for Streptococcus pyogenes","volume":"34","author":"Steer","year":"2016","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/infdis\/jiu260","article-title":"A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development","volume":"210","author":"Bessen","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1080\/21645515.2018.1462427","article-title":"Contribution of cryptic epitopes in designing a Group A Streptococcal vaccine","volume":"14","author":"Ozberk","year":"2018","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1016\/S0264-410X(02)00205-0","article-title":"Protection of mice from Group A Streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope","volume":"20","author":"Olive","year":"2002","journal-title":"Vaccine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1046\/j.1440-1711.2002.01067.x","article-title":"Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical Group A Streptococcal peptide vaccine candidate from the M protein using lipid-core peptide technology","volume":"80","author":"Hayman","year":"2002","journal-title":"Immunol. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8515","DOI":"10.1021\/jm301074n","article-title":"Structure-activity relationship for the development of a self-adjuvanting mucosally active lipopeptide vaccine against Streptococcus pyogenes","volume":"55","author":"Zaman","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/74719","article-title":"New multi-determinant strategy for a Group A Streptococcal vaccine designed for the Australian Aboriginal population","volume":"6","author":"Brandt","year":"2000","journal-title":"Nat. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1016\/j.vaccine.2007.01.079","article-title":"Comparative in silico analysis of two vaccine candidates for Group A Streptococcus predicts that they both may have similar safety profiles","volume":"25","author":"Shaila","year":"2007","journal-title":"Vaccine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.eurpolymj.2017.02.014","article-title":"The application of self-assembled nanostructures in peptide-based subunit vaccine development","volume":"93","author":"Zhao","year":"2017","journal-title":"Eur. Polym. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.2217\/nnm.14.187","article-title":"Recent advances in peptide-based subunit nanovaccines","volume":"9","author":"Skwarczynski","year":"2014","journal-title":"Nanomedicine (Lond.)"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1071\/CH11292","article-title":"Lipid peptide core nanoparticles as multivalent vaccine candidates against Streptococcus pyogenes","volume":"65","author":"Skwarczynski","year":"2012","journal-title":"Aust. J. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/978-1-61779-151-2_18","article-title":"Lipid-core-peptide system for self-adjuvanting synthetic vaccine delivery","volume":"Volume 751","author":"Mark","year":"2011","journal-title":"Bioconjugation Protocols"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1071\/CH09149","article-title":"Lipid core peptide system for gene, drug, and vaccine delivery","volume":"62","author":"Zhong","year":"2009","journal-title":"Aust. J. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1086\/374800","article-title":"Protection against Group A Streptococcus by immunization with J8-diphtheria toxoid: Contribution of J8-and diphtheria toxoid-specific antibodies to protection","volume":"187","author":"Batzloff","year":"2003","journal-title":"J. Infect. Dis"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.4049\/jimmunol.1202333","article-title":"Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help","volume":"190","author":"Pandey","year":"2013","journal-title":"J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sekuloski, S., Batzloff, M.R., Griffin, P., Parsonage, W., Elliott, S., Hartas, J., O\u2019Rourke, P., Marquart, L., Pandey, M., and Rubin, F.A. (2018). Evaluation of safety and immunogenicity of a Group A Streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198658"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0020-7519(01)00360-5","article-title":"Adapting immunity with subunit vaccines: Case studies with Group A Streptococcus and malaria","volume":"32","author":"Good","year":"2002","journal-title":"Int. J. Parasitol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.nano.2013.01.009","article-title":"An efficient, chemically-defined semisynthetic lipid-adjuvanted nanoparticulate vaccine development system","volume":"9","author":"Moyle","year":"2013","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nbt1179","article-title":"Characterization and identification of vaccine candidate proteins through analysis of the Group A Streptococcus surface proteome","volume":"24","author":"Norais","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1086\/380491","article-title":"Identification of new candidate vaccine antigens made by Streptococcus pyogenes: Purification and characterization of 16 putative extracellular lipoproteins","volume":"189","author":"Lei","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"M111","DOI":"10.1074\/mcp.M111.015693","article-title":"Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case","volume":"11","author":"Bensi","year":"2012","journal-title":"Mol. Cell. Proteom."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1128\/IAI.00295-10","article-title":"Novel conserved Group A Streptococcal proteins identified by the antigenome technology as vaccine candidates for a non-M protein-based vaccine","volume":"78","author":"Fritzer","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"34063","DOI":"10.18632\/oncotarget.6140","article-title":"The quest for GAS vaccine","volume":"6","author":"Pandey","year":"2015","journal-title":"Oncotarget"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.4049\/jimmunol.1501994","article-title":"Combinatorial synthetic peptide vaccine strategy protects against hypervirulent CovR\/S mutant Streptococci","volume":"196","author":"Pandey","year":"2016","journal-title":"J. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1365-2958.1995.mmi_17010137.x","article-title":"Characterization of a novel fibronectin-binding surface protein in Group A Streptococci","volume":"17","author":"Kreikemeyer","year":"1995","journal-title":"Mol. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7342","DOI":"10.1128\/IAI.72.12.7342-7345.2004","article-title":"Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model","volume":"72","author":"McArthur","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1086\/314655","article-title":"Protective immune response against Streptococcus pyogenes in mice after intranasal vaccination with the fibronectin-binding protein SfbI","volume":"179","author":"Guzman","year":"1999","journal-title":"J. Infect. Dis"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1128\/IAI.71.12.7197-7201.2003","article-title":"Identification of B- and T-cell epitopes within the fibronectin-binding domain of the SfbI protein of Streptococcus pyogenes","volume":"71","author":"Schulze","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1128\/iai.65.4.1357-1363.1997","article-title":"The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of Group A Streptococci by epithelial cells","volume":"65","author":"Molinari","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.1128\/iai.60.9.3837-3844.1992","article-title":"Fibronectin-binding protein of Streptococcus pyogenes: Sequence of the binding domain involved in adherence of streptococci to epithelial cells","volume":"60","author":"Talay","year":"1992","journal-title":"Infect. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.4049\/jimmunol.163.6.3396","article-title":"Fc-mediated nonspecific binding between fibronectin-binding protein of Streptococcus pyogenes and human immunoglobulins","volume":"163","author":"Medina","year":"1999","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/cmi.2009.10","article-title":"Similar ability of FbaA with M protein to elicit protective immunity against Group A Streptococcus challenge in mice","volume":"6","author":"Ma","year":"2009","journal-title":"Cell. Mol. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1128\/IAI.69.2.924-930.2001","article-title":"Systemic and mucosal immunizations with fibronectin-binding protein FBP54 induce protective immune responses against Streptococcus pyogenes challenge in mice","volume":"69","author":"Kawabata","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.nano.2017.08.015","article-title":"Bivalent mucosal peptide vaccines administered using the LCP carrier system stimulate protective immune responses against Streptococcus pyogenes infection","volume":"13","author":"Schulze","year":"2017","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1086\/603541","article-title":"Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection","volume":"200","author":"Turner","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.chom.2008.07.002","article-title":"The IL-8 protease SpyCEP\/ScpC of Group A Streptococcus promotes resistance to neutrophil killing","volume":"4","author":"Zinkernagel","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1016\/j.vaccine.2009.06.042","article-title":"Impact of immunization against SpyCEP during invasive disease with two Streptococcal species: Streptococcus pyogenes and Streptococcus equi","volume":"27","author":"Turner","year":"2009","journal-title":"Vaccine"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1128\/iai.65.6.2080-2087.1997","article-title":"Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization of mice by the Group A Streptococcus","volume":"65","author":"Ji","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1086\/377700","article-title":"Immune response to Group A Streptococcal C5a peptidase in children: implications for vaccine development","volume":"188","author":"Shet","year":"2003","journal-title":"J. Infect. Dis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7878","DOI":"10.1128\/IAI.73.12.7878-7886.2005","article-title":"Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils","volume":"73","author":"Park","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4332","DOI":"10.1016\/j.vaccine.2004.04.030","article-title":"Immunization with C5a peptidase from either Group A or B Streptococci enhances clearance of Group A Streptococci from intranasally infected mice","volume":"22","author":"Cleary","year":"2004","journal-title":"Vaccine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"15336","DOI":"10.1074\/jbc.274.22.15336","article-title":"Protein GRAB of streptococcus pyogenes regulates proteolysis at the bacterial surface by binding alpha2-macroglobulin","volume":"274","author":"Rasmussen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1128\/IAI.70.10.5363-5369.2002","article-title":"Immune responses to novel pneumococcal proteins pneumolysin, PspA, PsaA, and CbpA in adenoidal B cells from children","volume":"70","author":"Zhang","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1128\/jb.178.15.4688-4695.1996","article-title":"Insertional inactivation of Streptococcus pyogenes SOD suggests that prtF is regulated in response to a superoxide signal","volume":"178","author":"Gibson","year":"1996","journal-title":"J. Bacteriol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0928-8244(04)00003-3","article-title":"Immune response to superoxide dismutase in Group A Streptococcal infection","volume":"40","author":"McMillan","year":"2004","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1084\/jem.47.1.91","article-title":"The antigenic complex of Streptococcus haemolyticus: I. Demonstration of a type-specific substance in extracts of Streptococcus haemolyticus","volume":"47","author":"Lancefield","year":"1928","journal-title":"J. Exp. Med."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Caliot, E., Dramsi, S., Chapot-Chartier, M.P., Courtin, P., Kulakauskas, S., Pechoux, C., Trieu-Cuot, P., and Mistou, M.Y. (2012). Role of the Group B antigen of Streptococcus agalactiae: a peptidoglycan-anchored polysaccharide involved in cell wall biogenesis. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002756"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1084\/jem.96.6.569","article-title":"The lysis of Group A Hemolytic Streptococci by extracellular enzymes of Streptomyces albus. Nature of the cellular substrate attacked by the lytic enzymes","volume":"96","author":"McCarty","year":"1952","journal-title":"J. Exp. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.chom.2014.05.009","article-title":"The classical Lancefield antigen of Group A Streptococcus is a virulence determinant with implications for vaccine design","volume":"15","author":"Cole","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/213044a0","article-title":"Immunological relationship between Streptococcus A polysaccharide and the structural glycoproteins of heart valve","volume":"213","author":"Goldstein","year":"1967","journal-title":"Nature"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/219866a0","article-title":"Isolation from heart valves of glycopeptides which share immunological properties with Streptococcus haemolyticus group A polysaccharides","volume":"219","author":"Goldstein","year":"1968","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nm892","article-title":"Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea","volume":"9","author":"Kirvan","year":"2003","journal-title":"Nat. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/infdis\/171.3.593","article-title":"Group A Streptococcus-liposome ELISA antibody titers to group A polysaccharide and opsonophagocytic capabilities of the antibodies","volume":"171","author":"Salvadori","year":"1995","journal-title":"J. Infect. Dis"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1086\/498618","article-title":"Group A Streptococcus (GAS) carbohydrate as an immunogen for protection against GAS infection","volume":"193","author":"Sabharwal","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e02217","DOI":"10.1128\/mBio.02294-17","article-title":"Virulence role of the GlcNAc side chain of the Lancefield cell wall carbohydrate antigen in non-M1-serotype Group A Streptococcus","volume":"9","author":"Henningham","year":"2018","journal-title":"mBio"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.vaccine.2010.09.018","article-title":"Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate","volume":"29","author":"Kabanova","year":"2010","journal-title":"Vaccine"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1128\/MMBR.00028-16","article-title":"Lipoproteins of gram-positive bacteria: Key players in the immune response and virulence","volume":"80","author":"Nguyen","year":"2016","journal-title":"Microbiol. Mol. Biol. R."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Zaman, M., Abdel-Aal, A.B., Fujita, Y., Phillipps, K.S., Batzloff, M.R., Good, M.F., and Toth, I. (2012). Immunological evaluation of lipopeptide Group A Streptococcus (GAS) vaccine: structure-activity relationship. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030146"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Skwarczynski, M., Dougall, A.M., Khoshnejad, M., Chandrudu, S., Pearson, M.S., Loukas, A., and Toth, I. (2012). Peptide-based subunit vaccine against hookworm infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046870"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"399","DOI":"10.4161\/hv.27057","article-title":"Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine","volume":"10","author":"Dougall","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Hussein, W.M., Choi, P., Zhang, C., Su, M., Sierecki, E., Johnston, W., Fagan, V., Alexandrov, K., Skwarczynski, M., and Gambin, Y. (2016). Evaluation of lipopeptides as toll-like receptor 2 ligands. Curr. Drug Deliv.","DOI":"10.2174\/1567201813666160804114107"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00726-009-0463-0","article-title":"Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys","volume":"39","author":"Zeng","year":"2010","journal-title":"Amino Acids"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1517\/13543776.2014.880691","article-title":"Toll-like receptor agonists: A patent review (2011 - 2013)","volume":"24","author":"Hussein","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3389\/fimmu.2013.00318","article-title":"Immunostimulation by synthetic lipopeptide-based vaccine candidates: Structure-activity relationships","volume":"4","author":"Zaman","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1021\/acs.bioconjchem.7b00808","article-title":"Toll-like Receptor Agonist Conjugation: A Chemical Perspective","volume":"29","author":"Ignacio","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1023\/A:1016296106387","article-title":"A lipophilic adjuvant carrier system for antigenic peptides","volume":"8","author":"Horvath","year":"2001","journal-title":"Lett. Pept. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.bmcl.2018.03.042","article-title":"Site-specific effect of polar functional group-modification in lipids of TLR2 ligands for modulating the ligand immunostimulatory activity","volume":"28","author":"Arai","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1021\/bc500108b","article-title":"Site-specific incorporation of three toll-like receptor 2 targeting adjuvants into semisynthetic, molecularly defined nanoparticles: Application to Group A Streptococcal vaccines","volume":"25","author":"Moyle","year":"2014","journal-title":"Bioconjug. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1086\/505146","article-title":"Intranasal vaccination with a lipopeptide containing a conformationally constrained conserved minimal peptide, a universal T cell epitope, and a self-adjuvanting lipid protects mice from Group A Streptococcus challenge and reduces throat colonization","volume":"194","author":"Batzloff","year":"2006","journal-title":"J. Infect. Dis"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1021\/acsbiomaterials.6b00422","article-title":"Modular peptide amphiphile micelles improving an antibody-mediated immune response to Group A Streptococcus","volume":"3","author":"Barrett","year":"2017","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/cbic.201600639","article-title":"Synthesis, characterization and immunological evaluation of self-adjuvanting Group\u2005A Streptococcal vaccine candidates bearing various lipidic adjuvanting moieties","volume":"18","author":"Fagan","year":"2017","journal-title":"ChemBioChem"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9892","DOI":"10.1002\/chem.201801378","article-title":"Influence of physicochemical properties of lipopeptide adjuvants on the immune response: A rationale for engineering a potent vaccine","volume":"24","author":"Eskandari","year":"2018","journal-title":"Chem. Eur. J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1002\/chem.201404997","article-title":"Synthesis and characterisation of self-assembled and self-adjuvanting asymmetric multi-epitope lipopeptides of ovalbumin","volume":"21","author":"Eskandari","year":"2015","journal-title":"Chem. Eur. J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1016\/j.bmc.2016.03.063","article-title":"Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates","volume":"24","author":"Chan","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1073\/pnas.85.15.5409","article-title":"Synthetic peptide vaccine design: Synthesis and properties of a high-density multiple antigenic peptide system","volume":"85","author":"Tam","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","unstructured":"Skwarczynski, M., and Toth, I. (2017). Nanoparticle-based peptide vaccines. Micro and Nanotechnology in Vaccine Development, William Andrew Publishing."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bpj.2013.10.043","article-title":"Ligand mobility regulates B cell receptor clustering and signaling activation","volume":"106","author":"Ketchum","year":"2014","journal-title":"Biophys. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1128\/IAI.70.5.2734-2738.2002","article-title":"A lipid core peptide construct containing a conserved region determinant of the Group A Streptococcal M protein elicits heterologous opsonic antibodies","volume":"70","author":"Olive","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1016\/j.vaccine.2005.01.041","article-title":"Protection against Group A Streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides","volume":"23","author":"Olive","year":"2005","journal-title":"Vaccine"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1016\/j.vaccine.2009.12.046","article-title":"Structure-activity relationship of lipopeptide Group A Streptococcus (GAS) vaccine candidates on toll-like receptor 2","volume":"28","author":"Zaman","year":"2010","journal-title":"Vaccine"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1021\/jm701091d","article-title":"Structure-activity relationship of a series of synthetic lipopeptide self-adjuvanting Group A Streptococcal vaccine candidates","volume":"51","author":"Batzloff","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.2217\/nnm.14.190","article-title":"Group A Streptococcal vaccine candidate: Contribution of epitope to size, antigen presenting cell interaction and immunogenicity","volume":"9","author":"Zaman","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2174\/1567201813666160721141322","article-title":"Highly immunogenic trimethyl chitosan-based delivery system for intranasal lipopeptide vaccines against Group A Streptococcus","volume":"14","author":"Marasini","year":"2017","journal-title":"Curr. Drug Deliv."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.actbio.2016.04.012","article-title":"Liposome-based intranasal delivery of lipopeptide vaccine candidates against Group A Streptococcus","volume":"41","author":"Ghaffar","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1016\/j.tet.2009.02.060","article-title":"Development of highly pure alpha-helical lipoglycopeptides as self-adjuvanting vaccines","volume":"65","author":"Zhong","year":"2009","journal-title":"Tetrahedron"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1071\/CH09065","article-title":"Design and synthesis of lipopeptide-carbohydrate assembled multivalent vaccine candidates using native chemical ligation","volume":"62","author":"Zhong","year":"2009","journal-title":"Aust. J. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1021\/jm701410p","article-title":"Development of a liposaccharide-based delivery system and its application to the design of Group A Streptococcal vaccines","volume":"51","author":"Simerska","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/med.20191","article-title":"Modern lipid-, carbohydrate-, and peptide-based delivery systems for peptide, vaccine, and gene products","volume":"31","author":"Simerska","year":"2011","journal-title":"Med. Res. Rev."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/bip.20992","article-title":"Synthesis and in vivo studies of carbohydrate-based vaccines against Group A Streptococcus","volume":"90","author":"Simerska","year":"2008","journal-title":"Biopolymers"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"8907","DOI":"10.1016\/j.bmc.2008.08.064","article-title":"Synthesis and immunological evaluation of self-adjuvanting glycolipopeptide vaccine candidates","volume":"16","author":"Fujita","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4155\/tde-2016-0008","article-title":"Vaccine delivery: where polymer chemistry meets immunology","volume":"7","author":"Shae","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jconrel.2013.03.010","article-title":"Immune system targeting by biodegradable nanoparticles for cancer vaccines","volume":"168","author":"Silva","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jconrel.2007.05.034","article-title":"Effect of acidic pH on PLGA microsphere degradation and release","volume":"122","author":"Zolnik","year":"2007","journal-title":"J. Control. Release"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jconrel.2012.01.043","article-title":"PLGA-based nanoparticles: an overview of biomedical applications","volume":"161","author":"Danhier","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0169-409X(97)00048-3","article-title":"Biodegradation and biocompatibility of PLA and PLGA microspheres","volume":"28","author":"Shive","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"387023","DOI":"10.1155\/2013\/387023","article-title":"Chitin, chitosan, and glycated chitosan regulate immune responses: The novel adjuvants for cancer vaccine","volume":"2013","author":"Li","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_175","unstructured":"Skwarczynski, M., and Toth, I. (2017). Polymer-based nanoparticles as modern vaccine delivery systems. Micro and Nanotechnology in Vaccine Development, William Andrew Publishing."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.2217\/nnm-2016-0291","article-title":"Double adjuvanting strategy for peptide-based vaccines: Trimethyl chitosan nanoparticles for lipopeptide delivery","volume":"11","author":"Marasini","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.ijpharm.2016.09.057","article-title":"Lipid core peptide\/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A Streptococcus","volume":"513","author":"Marasini","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.actbio.2018.09.037","article-title":"Polyglutamic acid-trimethyl chitosan-based intranasal peptide nano-vaccine induces potent immune responses against Group A Streptococcus","volume":"80","author":"Nevagi","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1002\/anie.201002221","article-title":"Polyacrylate dendrimer nanoparticles: a self-adjuvanting vaccine delivery system","volume":"49","author":"Skwarczynski","year":"2010","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.nano.2010.10.002","article-title":"Self-adjuvanting polyacrylic nanoparticulate delivery system for Group A Streptococcus (GAS) vaccine","volume":"7","author":"Zaman","year":"2011","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2217\/nnm.13.7","article-title":"Polymer-peptide hybrids as a highly immunogenic single-dose nanovaccine","volume":"9","author":"Jia","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"601","DOI":"10.4155\/tde-2016-0037","article-title":"Linear and branched polyacrylates as a delivery platform for peptide-based vaccines","volume":"7","author":"Chandrudu","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrd1632","article-title":"Recent advances with liposomes as pharmaceutical carriers","volume":"4","author":"Torchilin","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1517\/17425247.2011.558081","article-title":"Liposomal vaccine delivery systems","volume":"8","author":"Korsholm","year":"2011","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0167-7799(00)89017-4","article-title":"Engineering liposomes for drug delivery: Progress and problems","volume":"13","author":"Gregoriadis","year":"1995","journal-title":"Trends Biotechnol."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Math\u00e9, G., Florentin, I., and Simmler, M.C. (1976). Liposomes as immunological adjuvants. Recent Results in Cancer Research, Springer. [1976\/01\/01 ed.].","DOI":"10.1007\/978-3-642-81017-6"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/252252a0","article-title":"Liposomes as immunological adjuvants","volume":"252","author":"Allison","year":"1974","journal-title":"Nature"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.2174\/1568026614666140329232757","article-title":"Liposomes as nanovaccine delivery systems","volume":"14","author":"Ghaffar","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Marasini, N., Ghaffar, K.A., Skwarczynski, M., and Toth, I. (2017). Liposomes as a Vaccine Delivery System, William Andrew Inc.","DOI":"10.1016\/B978-0-323-39981-4.00012-9"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.2217\/nnm.12.157","article-title":"Liposome-based delivery system for vaccine candidates: Constructing an effective formulation","volume":"7","author":"Giddam","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/erv.09.160","article-title":"Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists","volume":"9","author":"Black","year":"2010","journal-title":"Expert Rev. Vaccines"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"22","DOI":"10.2174\/1573406412666160720093138","article-title":"The role of size in development of mucosal liposome-lipopeptide vaccine candidates against Group A Streptococcus","volume":"13","author":"Ghaffar","year":"2016","journal-title":"Med. Chem."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Zaman, M., Ozberk, V., Langshaw, E.L., McPhun, V., Powell, J.L., Phillips, Z.N., Ho, M.F., Calcutt, A., Batzloff, M.R., and Toth, I. (2016). Novel platform technology for modular mucosal vaccine that protects against Streptococcus. Sci. Rep. UK, 6.","DOI":"10.1038\/srep39274"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/58\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:01:35Z","timestamp":1760187695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/58"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,1]]},"references-count":193,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["vaccines7030058"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7030058","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,1]]}}}