{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T03:51:00Z","timestamp":1775188260584,"version":"3.50.1"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> has been acquiring multiple drug resistance and has evolved into superbugs such as Methicillin\/Vancomycin-resistant <jats:italic>S. aureus<\/jats:italic> (MRSA\/VRSA) and, consequently, is a major cause of nosocomial and community infections associated with high morbidity and mortality for which no FDA-approved vaccines or biotherapeutics are available. Previous efforts targeting the surface-associated antigens have failed in clinical testing. Here, we generated hyperimmune products from sera in rabbits against six major <jats:italic>S. aureus<\/jats:italic> toxins targeted by an experimental vaccine (IBT-V02) and demonstrated significant efficacy for an anti-virulence passive immunization strategy. Extensive <jats:italic>in vitro<\/jats:italic> binding and neutralizing titers were analyzed against six extracellular toxins from individual animal sera. All IBT-V02 immunized animals elicited the maximum immune response upon the first boost dose against all pore-forming vaccine components, while for superantigen (SAgs) components of the vaccine, second and third doses of a boost were needed to reach a plateau in binding and toxin neutralizing titers. Importantly, both anti-staphylococcus hyperimmune products consisting of full-length IgG (IBT-V02-IgG) purified from the pooled sera and de-speciated F(ab\u2019)<jats:sub>2<\/jats:sub> (IBT-V02-F(ab\u2019)2) retained the binding and neutralizing titers against IBT-V02 target toxins. F(ab\u2019)<jats:sub>2<\/jats:sub> also exhibited cross-neutralization titers against three leukotoxins (HlgAB, HlgCB, and LukED) and four SAgs (SEC1, SED, SEK, and SEQ) which were not part of IBT-V02. F(ab\u2019)<jats:sub>2<\/jats:sub> also neutralized toxins in bacterial culture supernatant from major clinical strains of <jats:italic>S. aureus<\/jats:italic>. <jats:italic>In vivo<\/jats:italic> efficacy data generated in bacteremia and pneumonia models using USA300 <jats:italic>S. aureus<\/jats:italic> strain demonstrated dose-dependent protection by F(ab\u2019)<jats:sub>2<\/jats:sub>. These efficacy data confirmed the staphylococcal toxins as viable targets and support the further development effort of hyperimmune products as a potential adjunctive therapy for emergency uses against life-threatening <jats:italic>S. aureus<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fimmu.2022.893921","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T07:06:24Z","timestamp":1652771184000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Hyperimmune Targeting Staphylococcal Toxins Effectively Protect Against USA 300 MRSA Infection in Mouse Bacteremia and Pneumonia Models"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaobing","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Ortines","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ipsita","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tulasikumari","family":"Kanipakala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Kort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shardulendra P.","family":"Sherchand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Mednikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes L.","family":"Chenine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Javad","family":"Aman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cory L.","family":"Nykiforuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajan P.","family":"Adhikari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6809e1","article-title":"Vital Signs: Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections - United States","volume":"68","author":"Kourtis","year":"2019","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/1471-2334-14-296","article-title":"Incidence and Cost of Hospitalizations Associated With Staphylococcus Aureus Skin and Soft Tissue Infections in the United States From 2001 Through 2009","volume":"14","author":"Suaya","year":"2014","journal-title":"BMC Infect Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1086\/524891","article-title":"The Epidemic of Antibiotic-Resistant Infections: A Call to Action for the Medical Community From the Infectious Diseases Society of America","volume":"46","author":"Spellberg","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.1038\/s41598-019-42307-6","article-title":"Characterization of Infections With Vancomycin-Intermediate Staphylococcus Aureus (VISA) and Staphylococcus Aureus With Reduced Vancomycin Susceptibility in South Korea","volume":"9","author":"Park","year":"2019","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-020-03984-8","article-title":"Virulence Factors and Clonal Diversity of Staphylococcus Aureus in Colonization and Wound Infection With Emphasis on Diabetic Foot Infection","volume":"39","author":"Shettigar","year":"2020","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11060339","article-title":"Rational Design of Toxoid Vaccine Candidates for Staphylococcus Aureus Leukocidin AB (LukAB)","volume":"11","author":"Kailasan","year":"2019","journal-title":"Toxins (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1038\/s41598-019-39890-z","article-title":"TBA225, a Fusion Toxoid Vaccine for Protection and Broad Neutralization of Staphylococcal Superantigens","volume":"9","author":"Venkatasubramaniam","year":"2019","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.624310","article-title":"IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus Aureus","volume":"12","author":"Karauzum","year":"2021","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.03.110","article-title":"Status of Vaccine Research and Development of Vaccines for Staphylococcus Aureus","volume":"34","author":"Giersing","year":"2016","journal-title":"Vaccine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.3010","article-title":"Effect of an Investigational Vaccine for Preventing Staphylococcus Aureus Infections After Cardiothoracic Surgery: A Randomized Trial","volume":"309","author":"Fowler","year":"2013","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4161\/hv.34407","article-title":"Mortality Among Recipients of the Merck V710 Staphylococcus Aureus Vaccine After Postoperative S. Aureus Infections: An Analysis of Possible Contributing Host Factors","volume":"10","author":"McNeely","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.364075","article-title":"Synthetic Human Monoclonal Antibodies Toward Staphylococcal Enterotoxin B (SEB) Protective Against Toxic Shock Syndrome","volume":"287","author":"Karauzum","year":"2012","journal-title":"J Biol Chem"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit823","article-title":"Vaccination Against Staphylococcus Aureus Pneumonia","volume":"209","author":"Spaulding","year":"2014","journal-title":"J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis462","article-title":"Lower Antibody Levels to Staphylococcus Aureus Exotoxins Are Associated With Sepsis in Hospitalized Adults With Invasive S. Aureus Infections","volume":"206","author":"Adhikari","year":"2012","journal-title":"J Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit123","article-title":"A Serologic Correlate of Protective Immunity Against Community-Onset Staphylococcus Aureus Infection","volume":"56","author":"Fritz","year":"2013","journal-title":"Clin Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16897-9","article-title":"Risk and Outcome of Nosocomial Staphylococcus Aureus Bacteraemia in Nasal Carriers Versus Non-Carriers","volume":"364","author":"Wertheim","year":"2004","journal-title":"Lancet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"13296","DOI":"10.1038\/s41598-018-31424-3","article-title":"Hierarchy of Human IgG Recognition Within the Staphylococcus Aureus Immunome","volume":"8","author":"Radke","year":"2018","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.651619","article-title":"A Comprehensive View on the Human Antibody Repertoire Against Staphylococcus Aureus Antigens in the General Population","volume":"12","author":"Meyer","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8030072","article-title":"Targeting Staphylococcus Aureus Toxins: A Potential Form of Anti-Virulence Therapy","volume":"8","author":"Kong","year":"2016","journal-title":"Toxins (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.11.004","article-title":"Staphylococcus Aureus Toxins","volume":"17","author":"Otto","year":"2014","journal-title":"Curr Opin Microbiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01021-15","article-title":"Staphylococcus Aureus Biofilms Induce Macrophage Dysfunction Through Leukocidin AB and Alpha-Toxin","volume":"6","author":"Scherr","year":"2015","journal-title":"mBio"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2451","article-title":"A Staphylococcus Aureus Pore-Forming Toxin Subverts the Activity of ADAM10 to Cause Lethal Infection in Mice","volume":"17","author":"Inoshima","year":"2011","journal-title":"Nat Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/toxins5061140","article-title":"Staphylococcus Aureus Alpha-Toxin: Nearly a Century of Intrigue","volume":"5","author":"Berube","year":"2013","journal-title":"Toxins (Basel)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.27","article-title":"Leukocidins: Staphylococcal Bi-Component Pore-Forming Toxins Find Their Receptors","volume":"15","author":"Spaan","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10060252","article-title":"Staphylococcus Aureus Toxins and Their Molecular Activity in Infectious Diseases","volume":"10","author":"Oliveira","year":"2018","journal-title":"Toxins (Basel)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-018-5229-2","article-title":"Safety and Tolerability of a Single Administration of AR-301, a Human Monoclonal Antibody, in ICU Patients With Severe Pneumonia Caused by Staphylococcus Aureus: First-in-Human Trial","volume":"44","author":"Francois","year":"2018","journal-title":"Intensive Care Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.705360","article-title":"Staphylococcus Aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies","volume":"12","author":"Clegg","year":"2021","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01213-16","article-title":"Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus Aureus Necrotizing Pneumonia Upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin","volume":"60","author":"Diep","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186892","article-title":"Therapeutic Efficacy of Equine Botulism Antitoxin in Rhesus Macaques","volume":"12","author":"Kodihalli","year":"2017","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.24.20830","article-title":"Access to Diphtheria Antitoxin for Therapy and Diagnostics","volume":"19","author":"Both","year":"2014","journal-title":"Euro Surveill"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012416","article-title":"Characterization of Botulinum Neurotoxin Type A Neutralizing Monoclonal Antibodies and Influence of Their Half-Lives on Therapeutic Activity","volume":"5","author":"Mazuet","year":"2010","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9060180","article-title":"Role of Homologous Fc Fragment in the Potency and Efficacy of Anti-Botulinum Antibody Preparations","volume":"9","author":"Torgeman","year":"2017","journal-title":"Toxins (Basel)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137874","article-title":"Antibodies to S. Aureus LukS-PV Attenuated Subunit Vaccine Neutralize a Broad Spectrum of Canonical and Non-Canonical Bicomponent Leukotoxin Pairs","volume":"10","author":"Adhikari","year":"2015","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10090377","article-title":"A Critical Role for HlgA in Staphylococcus Aureus Pathogenesis Revealed by A Switch in the SaeRS Two-Component Regulatory System","volume":"10","author":"Venkatasubramaniam","year":"2018","journal-title":"Toxins (Basel)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00176-5","article-title":"Development of Engineered Vaccines Effective Against Structurally Related Bacterial Superantigens","volume":"16","author":"Ulrich","year":"1998","journal-title":"Vaccine"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.3.711","article-title":"Staphylococcal Enterotoxin A Has Two Cooperative Binding Sites on Major Histocompatibility Complex Class II","volume":"182","author":"Hudson","year":"1995","journal-title":"J Exp Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90088-8","article-title":"Multiple Binding Sites for Bacterial Superantigens on Soluble Class II MHC Molecules","volume":"3","author":"Kozono","year":"1995","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065384","article-title":"Structurally Designed Attenuated Subunit Vaccines for S. Aureus LukS-PV and LukF-PV Confer Protection in a Mouse Bacteremia Model","volume":"8","author":"Karauzum","year":"2013","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038567","article-title":"Novel Structurally Designed Vaccine for S. Aureus Alpha-Hemolysin: Protection Against Bacteremia and Pneumonia","volume":"7","author":"Adhikari","year":"2012","journal-title":"PloS One"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.621754","article-title":"Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus Aureus Vaccine in Rhesus Macaques","volume":"12","author":"Venkatasubramaniam","year":"2021","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028869","article-title":"Characterization of the Rabbit Neonatal Fc Receptor (FcRn) and Analyzing the Immunophenotype of the Transgenic Rabbits That Overexpresses FcRn","volume":"7","author":"Catunda Lemos","year":"2012","journal-title":"PloS One"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/antib8020028","article-title":"David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments","volume":"8","author":"Bates","year":"2019","journal-title":"Antibodies (Basel)"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1886560","DOI":"10.1080\/21645515.2021.1886560","article-title":"Polyclonal Hyper Immunoglobulin: A Proven Treatment and Prophylaxis Platform for Passive Immunization to Address Existing and Emerging Diseases","volume":"18","author":"Tharmalingam","year":"2022","journal-title":"Hum Vaccin Immunother"},{"key":"B44","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1146\/annurev-immunol-042718-041309","article-title":"Human Antibodies for Viral Infections","volume":"40","author":"Crowe","year":"2022","journal-title":"Annu Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100995","article-title":"A Requirement for FcgammaR in Antibody-Mediated Bacterial Toxin Neutralization","volume":"207","author":"Abboud","year":"2010","journal-title":"J Exp Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01007-14","article-title":"Isotype Switching Increases Efficacy of Antibody Protection Against Staphylococcal Enterotoxin B-Induced Lethal Shock and Staphylococcus Aureus Sepsis in Mice","volume":"5","author":"Varshney","year":"2014","journal-title":"mBio"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172229899","article-title":"Potent Neutralization of Botulinum Neurotoxin by Recombinant Oligoclonal Antibody","volume":"99","author":"Nowakowski","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuz030","article-title":"Development of a Vaccine Against Staphylococcus Aureus Invasive Infections: Evidence Based on Human Immunity, Genetics and Bacterial Evasion Mechanisms","volume":"44","author":"Miller","year":"2020","journal-title":"FEMS Microbiol Rev"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.462","article-title":"Genetic Requirement for ADAM10 in Severe Staphylococcus Aureus Skin Infection","volume":"132","author":"Inoshima","year":"2012","journal-title":"J Invest Dermatol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis192","article-title":"ADAM10 Mediates Vascular Injury Induced by Staphylococcus Aureus Alpha-Hemolysin","volume":"206","author":"Powers","year":"2012","journal-title":"J Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"491401","DOI":"10.1155\/2008\/491401","article-title":"Necrotizing Pneumonia Caused by Panton-Valentine Leucocidin-Producing Staphylococcus Aureus Originating From a Bartholin's Abscess","volume":"2008","author":"Jung","year":"2008","journal-title":"Infect Dis Obstet Gynecol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268815001521","article-title":"Necrotizing Pneumonia Due to Clonally Diverse Staphylococcus Aureus Strains Producing Panton-Valentine Leukocidin: The Czech Experience","volume":"144","author":"Rajova","year":"2016","journal-title":"Epidemiol Infect"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/toxins6030950","article-title":"Staphylococcal Bicomponent Pore-Forming Toxins: Targets for Prophylaxis and Immunotherapy","volume":"6","author":"Aman","year":"2014","journal-title":"Toxins (Basel)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1128\/MMBR.00055-13","article-title":"The Bicomponent Pore-Forming Leucocidins of Staphylococcus Aureus","volume":"78","author":"Alonzo","year":"2014","journal-title":"Microbiol Mol Biol Rev"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2016.1215791","article-title":"Context Matters: The Importance of Dimerization-Induced Conformation of the LukGH Leukocidin of Staphylococcus Aureus for the Generation of Neutralizing Antibodies","volume":"8","author":"Badarau","year":"2016","journal-title":"MAbs"},{"key":"B56","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s44149-021-00007-7","article-title":"Update on Molecular Diversity and Multipathogenicity of Staphylococcal Superantigen Toxins","volume":"1","author":"Hu","year":"2021","journal-title":"Anim Diseases"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00104-12","article-title":"Staphylococcal and Streptococcal Superantigen Exotoxins","volume":"26","author":"Spaulding","year":"2013","journal-title":"Clin Microbiol Rev"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1086\/657156","article-title":"Staphylococcal Superantigens Cause Lethal Pulmonary Disease in Rabbits","volume":"202","author":"Strandberg","year":"2010","journal-title":"J Infect Dis"},{"key":"B59","doi-asserted-by":"publisher","first-page":"103588","DOI":"10.1016\/j.fm.2020.103588","article-title":"A Novel Staphylococcal Enterotoxin SE02 Involved in a Staphylococcal Food Poisoning Outbreak That Occurred in Tokyo in 2004","volume":"92","author":"Suzuki","year":"2020","journal-title":"Food Microbiol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11030178","article-title":"Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock","volume":"11","author":"Krakauer","year":"2019","journal-title":"Toxins (Basel)"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2006.12.004","article-title":"Superantigen-Induced Cytokine Release From Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy After Oral Dosing in Nonhuman Primates","volume":"83","author":"Krakauer","year":"2007","journal-title":"Res Vet Sci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013253","article-title":"Inhibition of Toxic Shock by Human Monoclonal Antibodies Against Staphylococcal Enterotoxin B","volume":"5","author":"Larkin","year":"2010","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1086\/320732","article-title":"Inhibition of Staphylococcal Enterotoxin A-Induced Superantigenic and Lethal Activities by a Monoclonal Antibody to Toxic Shock Syndrome Toxin-1","volume":"183","author":"Kum","year":"2001","journal-title":"J Infect Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02183-15","article-title":"Demography and Intercontinental Spread of the USA300 Community-Acquired Methicillin-Resistant Staphylococcus Aureus Lineage","volume":"7","author":"Glaser","year":"2016","journal-title":"mBio"},{"key":"B65","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s10142-005-0019-7","article-title":"Understanding the Rise of the Superbug: Investigation of the Evolution and Genomic Variation of Staphylococcus Aureus","volume":"6","author":"Lindsay","year":"2006","journal-title":"Funct Integr Genomics"},{"key":"B66","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.femsre.2003.09.003","article-title":"Regulation of Virulence Determinants in Staphylococcus Aureus: Complexity and Applications","volume":"28","author":"Bronner","year":"2004","journal-title":"FEMS Microbiol Rev"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03526.x","article-title":"Autoinduction and Signal Transduction in the Regulation of Staphylococcal Virulence","volume":"48","author":"Novick","year":"2003","journal-title":"Mol Microbiol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1086\/655396","article-title":"Clinical Correlates of Panton-Valentine Leukocidin (PVL), PVL Isoforms, and Clonal Complex in the Staphylococcus Aureus Population of Northern Australia","volume":"202","author":"Tong","year":"2010","journal-title":"J Infect Dis"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00071-16","article-title":"Phenotypes and Virulence Among Staphylococcus Aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages","volume":"1","author":"King","year":"2016","journal-title":"mSphere"},{"key":"B70","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1574-695X.2012.00937.x","article-title":"Virulence Strategies of the Dominant USA300 Lineage of Community-Associated Methicillin-Resistant Staphylococcus Aureus (CA-MRSA)","volume":"65","author":"Thurlow","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3201\/eid2111.150452","article-title":"USA300 Methicillin-Resistant Staphylococcus Aureus, United States, 2000-2013","volume":"21","author":"Carrel","year":"2015","journal-title":"Emerg Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.893921\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T07:06:32Z","timestamp":1652771192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.893921\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":71,"alternative-id":["10.3389\/fimmu.2022.893921"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.893921","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]},"article-number":"893921"}}