{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:45:13Z","timestamp":1791747913948,"version":"4.3.4"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The upper respiratory tract (URT) is the major entry site for human pathogens and strategies to activate this network could lead to new vaccines capable of preventing infection with many pathogens. Group A streptococcus (GAS) infections, causing rheumatic fever, rheumatic heart disease, and invasive disease, are responsible for substantial morbidity and mortality. We describe an innovative vaccine strategy to induce mucosal antibodies of significant magnitude against peptide antigens of GAS using a novel biocompatible liposomal platform technology. The approach is to encapsulate free diphtheria toxoid (DT), a standard vaccine antigen, within liposomes as a source of helper T-cell stimulation while lipidated peptide targets for B-cells are separately displayed on the liposome surface. As DT is not physically conjugated to the peptide, it is possible to develop modular epitopic constructs that simultaneously activate IgA-producing B-cells of different and complementary specificity and function that together neutralize distinct virulence factors. An inflammatory cellular immune response is also induced. The immune response provides profound protection against streptococcal infection in the URT. The study describes a new vaccine platform for humoral and cellular immunity applicable to the development of vaccines against multiple mucosal pathogens.<\/jats:p>","DOI":"10.1038\/srep39274","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T13:23:56Z","timestamp":1481808236000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Novel platform technology for modular mucosal vaccine that protects against streptococcus"],"prefix":"10.1038","volume":"6","author":[{"given":"Mehfuz","family":"Zaman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Ozberk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Langshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"McPhun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary N.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Fong","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainslie","family":"Calcutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Batzloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Toth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey R.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Good","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"BFsrep39274_CR1","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1001\/jama.1997.03550110039033","volume":"278","author":"R Gonzales","year":"1997","unstructured":"Gonzales, R., Steiner, J. F. & Sande, M. A. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. Jama 278, 901\u2013904 (1997).","journal-title":"Jama"},{"key":"BFsrep39274_CR2","doi-asserted-by":"crossref","unstructured":"Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet385, 117\u2013171, doi: 10.1016\/s0140-6736(14)61682-2 (2015).","DOI":"10.1016\/S0140-6736(14)61682-2"},{"key":"BFsrep39274_CR3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1097\/INF.0b013e318281da11","volume":"32","author":"AC Steer","year":"2013","unstructured":"Steer, A. C., Dale, J. B. & Carapetis, J. R. Progress toward a global group a streptococcal vaccine. Pediatr Infect Dis J 32, 180\u2013182, doi: 10.1097\/INF.0b013e318281da11 (2013).","journal-title":"Pediatr Infect Dis J"},{"key":"BFsrep39274_CR4","doi-asserted-by":"publisher","first-page":"402","DOI":"10.4161\/viru.2.5.16342","volume":"2","author":"D Metzgar","year":"2011","unstructured":"Metzgar, D. & Zampolli, A. The M protein of group A Streptococcus is a key virulence factor and a clinically relevant strain identification marker. Virulence 2, 402\u2013412, doi: 10.4161\/viru.2.5.16342 (2011).","journal-title":"Virulence"},{"key":"BFsrep39274_CR5","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1016\/j.vaccine.2013.01.019","volume":"31","author":"JB Dale","year":"2013","unstructured":"Dale, J. B. et al. Potential coverage of a multivalent M protein-based group A streptococcal vaccine. Vaccine 31, 1576\u20131581, doi: 10.1016\/j.vaccine.2013.01.019 (2013).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR6","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1086\/374800","volume":"187","author":"MR Batzloff","year":"2003","unstructured":"Batzloff, M. R. et al. Protection against group A streptococcus by immunization with J8-diphtheria toxoid: contribution of J8- and diphtheria toxoid-specific antibodies to protection. The Journal of infectious diseases 187, 1598\u20131608, doi: 10.1086\/374800 (2003).","journal-title":"The Journal of infectious diseases"},{"key":"BFsrep39274_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40256-013-0005-8","volume":"13","author":"L Guilherme","year":"2013","unstructured":"Guilherme, L., Ferreira, F. M., Kohler, K. F., Postol, E. & Kalil, J. A vaccine against Streptococcus pyogenes: the potential to prevent rheumatic fever and rheumatic heart disease. Am J Cardiovasc Drugs 13, 1\u20134, doi: 10.1007\/s40256-013-0005-8 (2013).","journal-title":"Am J Cardiovasc Drugs"},{"key":"BFsrep39274_CR8","doi-asserted-by":"publisher","first-page":"4923","DOI":"10.1016\/j.vaccine.2009.06.042","volume":"27","author":"CE Turner","year":"2009","unstructured":"Turner, C. E., Kurupati, P., Wiles, S., Edwards, R. J. & Sriskandan, S. Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi. Vaccine 27, 4923\u20134929, doi: 10.1016\/j.vaccine.2009.06.042 (2009).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR9","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1086\/377700","volume":"188","author":"A Shet","year":"2003","unstructured":"Shet, A., Kaplan, E. L., Johnson, D. R. & Cleary, P. P. Immune response to group A streptococcal C5a peptidase in children: implications for vaccine development. J Infect Dis 188, 809\u2013817, doi: 10.1086\/377700 (2003).","journal-title":"J Infect Dis"},{"key":"BFsrep39274_CR10","doi-asserted-by":"publisher","first-page":"6038","DOI":"10.1016\/j.bmcl.2013.09.042","volume":"23","author":"FI Auzanneau","year":"2013","unstructured":"Auzanneau, F. I., Borrelli, S. & Pinto, B. M. Synthesis and immunological activity of an oligosaccharide-conjugate as a vaccine candidate against Group A Streptococcus. Bioorg Med Chem Lett 23, 6038\u20136042, doi: 10.1016\/j.bmcl.2013.09.042 (2013).","journal-title":"Bioorg Med Chem Lett"},{"key":"BFsrep39274_CR11","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1093\/intimm\/9.11.1723","volume":"9","author":"WA Hayman","year":"1997","unstructured":"Hayman, W. A. et al. 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. Int Immunol 9, 1723\u20131733 (1997).","journal-title":"Int Immunol"},{"key":"BFsrep39274_CR12","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.4049\/jimmunol.1501994","volume":"196","author":"M Pandey","year":"2016","unstructured":"Pandey, M. & Mortensen, R. Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR\/S Mutant Streptococci. 196, 3364\u20133374, doi: 10.4049\/jimmunol.1501994 (2016).","journal-title":"Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR\/S Mutant Streptococci"},{"key":"BFsrep39274_CR13","doi-asserted-by":"publisher","first-page":"5915","DOI":"10.4049\/jimmunol.1500157","volume":"194","author":"M Pandey","year":"2015","unstructured":"Pandey, M. et al. A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia. J Immunol 194, 5915\u20135925, doi: 10.4049\/jimmunol.1500157 (2015).","journal-title":"J Immunol"},{"key":"BFsrep39274_CR14","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1084\/jem.167.6.1945","volume":"167","author":"D Bessen","year":"1988","unstructured":"Bessen, D. & Fischetti, V. A. Passive acquired mucosal immunity to group A streptococci by secretory immunoglobulin A. J Exp Med 167, 1945\u20131950 (1988).","journal-title":"J Exp Med"},{"key":"BFsrep39274_CR15","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1086\/466528","volume":"192","author":"MR Batzloff","year":"2005","unstructured":"Batzloff, M. R. et al. Toward the development of an antidisease, transmission-blocking intranasal vaccine for group a streptococcus. J Infect Dis 192, 1450\u20131455, doi: 10.1086\/466528 (2005).","journal-title":"J Infect Dis"},{"key":"BFsrep39274_CR16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4110\/in.2015.15.2.51","volume":"15","author":"S Lee","year":"2015","unstructured":"Lee, S. & Nguyen, M. T. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw 15, 51\u201357, doi: 10.4110\/in.2015.15.2.51 (2015).","journal-title":"Immune Netw"},{"key":"BFsrep39274_CR17","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1111\/j.0818-9641.2004.01280.x","volume":"82","author":"SA Moschos","year":"2004","unstructured":"Moschos, S. A., Bramwell, V. W., Somavarapu, S. & Alpar, H. O. Adjuvant synergy: the effects of nasal coadministration of adjuvants. Immunol Cell Biol 82, 628\u2013637, doi: 10.1111\/j.0818-9641.2004.01280.x (2004).","journal-title":"Immunol Cell Biol"},{"key":"BFsrep39274_CR18","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1517\/13543776.2014.880691","volume":"24","author":"WM Hussein","year":"2014","unstructured":"Hussein, W. M., Liu, T. Y., Skwarczynski, M. & Toth, I. Toll-like receptor agonists: a patent review (2011 - 2013). Expert Opin Ther Pat 24, 453\u2013470, doi: 10.1517\/13543776.2014.880691 (2014).","journal-title":"Expert Opin Ther Pat"},{"key":"BFsrep39274_CR19","doi-asserted-by":"publisher","first-page":"318","DOI":"10.3389\/fimmu.2013.00318","volume":"4","author":"M Zaman","year":"2013","unstructured":"Zaman, M. & Toth, I. Immunostimulation by synthetic lipopeptide-based vaccine candidates: structure-activity relationships. Front Immunol 4, 318, doi: 10.3389\/fimmu.2013.00318 (2013).","journal-title":"Front Immunol"},{"key":"BFsrep39274_CR20","doi-asserted-by":"crossref","unstructured":"Tandrup Schmidt, S., Foged, C., Korsholm, K. S., Rades, T. & Christensen, D. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators. Pharmaceutics 8, doi: 10.3390\/pharmaceutics8010007 (2016).","DOI":"10.3390\/pharmaceutics8010007"},{"key":"BFsrep39274_CR21","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1016\/j.vaccine.2012.01.070","volume":"30","author":"DS Watson","year":"2012","unstructured":"Watson, D. S., Endsley, A. N. & Huang, L. Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. Vaccine 30, 2256\u20132272, doi: 10.1016\/j.vaccine.2012.01.070 (2012).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR22","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.2217\/nnm.12.157","volume":"7","author":"AK Giddam","year":"2012","unstructured":"Giddam, A. K., Zaman, M., Skwarczynski, M. & Toth, I. Liposome-based delivery system for vaccine candidates: constructing an effective formulation. Nanomedicine (Lond) 7, 1877\u20131893, doi: 10.2217\/nnm.12.157 (2012).","journal-title":"Nanomedicine (Lond)"},{"key":"BFsrep39274_CR23","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nri3469","volume":"13","author":"MI Yuseff","year":"2013","unstructured":"Yuseff, M. I., Pierobon, P., Reversat, A. & Lennon-Dumenil, A. M. How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol 13, 475\u2013486, doi: 10.1038\/nri3469 (2013).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep39274_CR24","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/nchembio.2007.25","volume":"3","author":"S Ingale","year":"2007","unstructured":"Ingale, S., Wolfert, M. A., Gaekwad, J., Buskas, T. & Boons, G. J. Robust immune responses elicited by a fully synthetic three-component vaccine. Nat Chem Biol 3, 663\u2013667, doi: 10.1038\/nchembio.2007.25 (2007).","journal-title":"Nat Chem Biol"},{"key":"BFsrep39274_CR25","doi-asserted-by":"publisher","first-page":"7878","DOI":"10.1128\/iai.73.12.7878-7886.2005","volume":"73","author":"HS Park","year":"2005","unstructured":"Park, H. S. & Cleary, P. P. 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. Infect Immun 73, 7878\u20137886, doi: 10.1128\/iai.73.12.7878-7886.2005 (2005).","journal-title":"Infect Immun"},{"key":"BFsrep39274_CR26","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/nri2868","volume":"10","author":"MF Bachmann","year":"2010","unstructured":"Bachmann, M. F. & Jennings, G. T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10, 787\u2013796, doi: 10.1038\/nri2868 (2010).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep39274_CR27","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/icb.2014.21","volume":"92","author":"S Neumann","year":"2014","unstructured":"Neumann, S. et al. Activation of the NLRP3 inflammasome is not a feature of all particulate vaccine adjuvants. Immunol Cell Biol 92, 535\u2013542, doi: 10.1038\/icb.2014.21 (2014).","journal-title":"Immunol Cell Biol"},{"key":"BFsrep39274_CR28","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1038\/ncomms2608","volume":"4","author":"Z Zhong","year":"2013","unstructured":"Zhong, Z. et al. TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nat Commun 4, 1611, doi: 10.1038\/ncomms2608 (2013).","journal-title":"Nat Commun"},{"key":"BFsrep39274_CR29","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/1556-276x-8-102","volume":"8","author":"A Akbarzadeh","year":"2013","unstructured":"Akbarzadeh, A. et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett 8, 102, doi: 10.1186\/1556-276x-8-102 (2013).","journal-title":"Nanoscale Res Lett"},{"key":"BFsrep39274_CR30","doi-asserted-by":"publisher","first-page":"3978","DOI":"10.1182\/blood-2007-10-119636","volume":"111","author":"F Walker","year":"2008","unstructured":"Walker, F. et al. IL6\/sIL6R complex contributes to emergency granulopoietic responses in G-CSF- and GM-CSF-deficient mice. Blood 111, 3978\u20133985, doi: 10.1182\/blood-2007-10-119636 (2008).","journal-title":"Blood"},{"key":"BFsrep39274_CR31","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1093\/intimm\/11.4.569","volume":"11","author":"ER Brandt","year":"1999","unstructured":"Brandt, E. R. et al. Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities. Int Immunol 11, 569\u2013576 (1999).","journal-title":"Int Immunol"},{"key":"BFsrep39274_CR32","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1084\/jem.169.6.2133","volume":"169","author":"KW Beagley","year":"1989","unstructured":"Beagley, K. W. et al. Interleukins and IgA synthesis. Human and murine interleukin 6 induce high rate IgA secretion in IgA-committed B cells. J Exp Med 169, 2133\u20132148 (1989).","journal-title":"J Exp Med"},{"key":"BFsrep39274_CR33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4049\/jimmunol.156.2.558","volume":"156","author":"AK Yi","year":"1996","unstructured":"Yi, A. K., Chace, J. H., Cowdery, J. S. & Krieg, A. M. IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides. J Immunol 156, 558\u2013564 (1996).","journal-title":"J Immunol"},{"key":"BFsrep39274_CR34","doi-asserted-by":"crossref","unstructured":"Ghaffar, K. A. et al. Liposome-based Intranasal Delivery of Lipopeptide Vaccine Candidates Against Group A Streptococcus. Acta Biomater, doi: 10.1016\/j.actbio.2016.04.012 (2016).","DOI":"10.1016\/j.actbio.2016.04.012"},{"key":"BFsrep39274_CR35","doi-asserted-by":"publisher","first-page":"8515","DOI":"10.1021\/jm301074n","volume":"55","author":"M Zaman","year":"2012","unstructured":"Zaman, M. et al. Structure-activity relationship for the development of a self-adjuvanting mucosally active lipopeptide vaccine against Streptococcus pyogenes. J Med Chem 55, 8515\u20138523, doi: 10.1021\/jm301074n (2012).","journal-title":"J Med Chem"},{"key":"BFsrep39274_CR36","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/0264-410X(94)00058-U","volume":"13","author":"WI White","year":"1995","unstructured":"White, W. I. et al. Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen. Vaccine 13, 1111\u20131122 (1995).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR37","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1016\/S0264-410X(02)00261-X","volume":"20","author":"A Ninomiya","year":"2002","unstructured":"Ninomiya, A., Ogasawara, K., Kajino, K., Takada, A. & Kida, H. Intranasal administration of a synthetic peptide vaccine encapsulated in liposome together with an anti-CD40 antibody induces protective immunity against influenza A virus in mice. Vaccine 20, 3123\u20133129 (2002).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR38","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.4049\/jimmunol.142.5.1437","volume":"142","author":"P Dal Monte","year":"1989","unstructured":"Dal Monte, P. & Szoka, F. C., Jr. Effect of liposome encapsulation on antigen presentation in vitro. Comparison of presentation by peritoneal macrophages and B cell tumors. J Immunol 142, 1437\u20131443 (1989).","journal-title":"J Immunol"},{"key":"BFsrep39274_CR39","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/0092-8674(91)90647-H","volume":"64","author":"CV Harding","year":"1991","unstructured":"Harding, C. V., Collins, D. S., Slot, J. W., Geuze, H. J. & Unanue, E. R. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Cell 64, 393\u2013401 (1991).","journal-title":"Cell"},{"key":"BFsrep39274_CR40","doi-asserted-by":"publisher","first-page":"e1002252","DOI":"10.1371\/journal.ppat.1002252","volume":"7","author":"T Dileepan","year":"2011","unstructured":"Dileepan, T. et al. Robust antigen specific th17 T cell response to group A Streptococcus is dependent on IL-6 and intranasal route of infection. PLoS Pathog 7, e1002252, doi: 10.1371\/journal.ppat.1002252 (2011).","journal-title":"PLoS Pathog"},{"key":"BFsrep39274_CR41","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1172\/jci80792","volume":"126","author":"T Dileepan","year":"2016","unstructured":"Dileepan, T. et al. Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells. J Clin Invest 126, 303\u2013317, doi: 10.1172\/jci80792 (2016).","journal-title":"J Clin Invest"},{"key":"BFsrep39274_CR42","doi-asserted-by":"publisher","first-page":"14215","DOI":"10.1074\/jbc.M513408200","volume":"281","author":"Y Terao","year":"2006","unstructured":"Terao, Y., Yamaguchi, M., Hamada, S. & Kawabata, S. Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. J Biol Chem 281, 14215\u201314223, doi: 10.1074\/jbc.M513408200 (2006).","journal-title":"J Biol Chem"},{"key":"BFsrep39274_CR43","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1056\/NEJMoa030595","volume":"350","author":"M Mutsch","year":"2004","unstructured":"Mutsch, M. et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell\u2019s palsy in Switzerland. N Engl J Med 350, 896\u2013903, doi: 10.1056\/NEJMoa030595 (2004).","journal-title":"N Engl J Med"},{"key":"BFsrep39274_CR44","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1056\/NEJMp048006","volume":"350","author":"RB Couch","year":"2004","unstructured":"Couch, R. B. Nasal vaccination, Escherichia coli enterotoxin, and Bell\u2019s palsy. N Engl J Med 350, 860\u2013861, doi: 10.1056\/NEJMp048006 (2004).","journal-title":"N Engl J Med"},{"key":"BFsrep39274_CR45","doi-asserted-by":"publisher","first-page":"e6999","DOI":"10.1371\/journal.pone.0006999","volume":"4","author":"DJ Lewis","year":"2009","unstructured":"Lewis, D. J. et al. Transient facial nerve paralysis (Bell\u2019s palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS One 4, e6999, doi: 10.1371\/journal.pone.0006999 (2009).","journal-title":"PLoS One"},{"key":"BFsrep39274_CR46","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1146\/annurev.bb.09.060180.002343","volume":"9","author":"F Szoka Jr.","year":"1980","unstructured":"Szoka, F., Jr. & Papahadjopoulos, D. Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng 9, 467\u2013508, doi: 10.1146\/annurev.bb.09.060180.002343 (1980).","journal-title":"Annu Rev Biophys Bioeng"},{"key":"BFsrep39274_CR47","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.2217\/nnm.14.190","volume":"9","author":"M Zaman","year":"2014","unstructured":"Zaman, M. et al. Group A Streptococcal vaccine candidate: contribution of epitope to size, antigen presenting cell interaction and immunogenicity. Nanomedicine (Lond) 9, 2613\u20132624, doi: 10.2217\/nnm.14.190 (2014).","journal-title":"Nanomedicine (Lond)"},{"key":"BFsrep39274_CR48","doi-asserted-by":"publisher","first-page":"2816","DOI":"10.1016\/S0264-410X(02)00205-0","volume":"20","author":"C Olive","year":"2002","unstructured":"Olive, C., Clair, T., Yarwood, P. & Good, M. F. 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. Vaccine 20, 2816\u20132825 (2002).","journal-title":"Vaccine"},{"key":"BFsrep39274_CR49","doi-asserted-by":"publisher","first-page":"e61655","DOI":"10.1371\/journal.pone.0061655","volume":"8","author":"FM Alam","year":"2013","unstructured":"Alam, F. M., Turner, C. E., Smith, K., Wiles, S. & Sriskandan, S. Inactivation of the CovR\/S virulence regulator impairs infection in an improved murine model of Streptococcus pyogenes naso-pharyngeal infection. PLoS One 8, e61655, doi: 10.1371\/journal.pone.0061655 (2013).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39274.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39274","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39274.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:46:36Z","timestamp":1672886796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39274"],"URL":"https:\/\/doi.org\/10.1038\/srep39274","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]},"assertion":[{"value":"10 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.Z. and M.F.G. are inventors on patents related to the liposome technology. These patents have been licensed to Olymvax Biopharmaceuticals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39274"}}