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Research Paper

Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial

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Pages 620-631 | Received 21 Aug 2014, Accepted 16 Nov 2014, Published online: 03 Apr 2015

References

  • Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339:520-32; PMID:9709046; http://dx.doi.org/10.1056/NEJM199808203390806
  • Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 2006; 368:874-85; PMID:16950365; http://dx.doi.org/10.1016/S0140-6736(06)68853-3
  • WHO. Antimicrobial resistance. Fact sheet N°194. Updated May 2013. Available at: http://www.who.int/mediacentre/factsheets/fs194/en/
  • Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, van Keulen PH, Vandenbroucke-Grauls CM, Meester MH, Verbrugh HA. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 2004; 364:703-5; PMID:15325835; http://dx.doi.org/10.1016/S0140-6736(04)16897-9
  • Bagnoli F, Bertholet S, Grandi G. Inferring reasons for the failure of Staphylococcus aureus vaccines in clinical trials. Front Cell Infect Microbiol 2012; 2:16; PMID:22919608; http://dx.doi.org/10.3389/fcimb.2012.00016
  • Thakker M, Park JS, Carey V, Lee JC. Staphylococcus aureus serotype 5 capsular polysaccharide is antiphagocytic and enhances bacterial virulence in a murine bacteremia model. Infect Immun 1998; 66:5183-9; PMID:9784520
  • Foster TJ, Geoghegan JA, Ganesh VK, Hook M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 2014; 12:49-62; PMID:24336184; http://dx.doi.org/10.1038/nrmicro3161
  • Novick RP. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol Microbiol 2003; 48:1429-49; PMID:12791129; http://dx.doi.org/10.1046/j.1365-2958.2003.03526.x
  • O'Riordan K, Lee JC. Staphylococcus aureus capsular polysaccharides. Clin Microbiol Rev 2004; 17:218-34; PMID:14726462; http://dx.doi.org/10.1128/CMR.17.1.218-234.2004
  • Foster TJ. Immune evasion by staphylococci. Nat Rev Microbiol 2005; 3:948-58; PMID:16322743; http://dx.doi.org/10.1038/nrmicro1289
  • Hair PS, Ward MD, Semmes OJ, Foster TJ, Cunnion KM. Staphylococcus aureus clumping factor A binds to complement regulator factor I and increases factor I cleavage of C3b. J Infect Dis 2008; 198:125-33; PMID:18544012; http://dx.doi.org/10.1086/588825
  • McCormick JK, Yarwood JM, Schlievert PM. Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol 2001; 55:77-104; PMID:11544350; http://dx.doi.org/10.1146/annurev.micro.55.1.77
  • Postma B, Kleibeuker W, Poppelier MJ, Boonstra M, Van Kessel KP, Van Strijp JA, de Haas CJ. Residues 10-18 within the C5a receptor N terminus compose a binding domain for chemotaxis inhibitory protein of Staphylococcus aureus. J Biol Chem 2005; 280:2020-7; PMID:15542591; http://dx.doi.org/10.1074/jbc.M412230200
  • Silverman GJ, Goodyear CS. Confounding B-cell defences: lessons from a staphylococcal superantigen. Nat Rev Immunol 2006; 6:465-75; PMID:16724100; http://dx.doi.org/10.1038/nri1853
  • Peterson PK, Verhoef J, Sabath LD, Quie PG. Effect of protein A on staphylococcal opsonization. Infect Immun 1977; 15:760-4; PMID:870431
  • Wang J, Roderiquez G, Norcross MA. Control of adaptive immune responses by Staphylococcus aureus through IL-10, PD-L1, and TLR2. Sci Rep 2012; 2:606; PMID:22930672
  • Kim HK, Thammavongsa V, Schneewind O, Missiakas D. Recurrent infections and immune evasion strategies of Staphylococcus aureus. Curr Opin Microbiol 2012; 15:92-9; PMID:22088393; http://dx.doi.org/10.1016/j.mib.2011.10.012
  • Proctor RA, von Eiff C, Kahl BC, Becker K, McNamara P, Herrmann M, Peters G. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006; 4:295-305; PMID:16541137; http://dx.doi.org/10.1038/nrmicro1384
  • Thurlow LR, Hanke ML, Fritz T, Angle A, Aldrich A, Williams SH, Engebretsen IL, Bayles KW, Horswill AR, Kielian T. Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J Immunol 2011; 186:6585-96; PMID:21525381; http://dx.doi.org/10.4049/jimmunol.1002794
  • Proctor RA. Is there a future for a Staphylococcus aureus vaccine? Vaccine 2012; 30:2921-7; PMID:22115633; http://dx.doi.org/10.1016/j.vaccine.2011.11.006
  • Schaffer AC, Lee JC. Staphylococcal vaccines and immunotherapies. Infect Dis Clin North Am 2009; 23:153-71; PMID:19135920; http://dx.doi.org/10.1016/j.idc.2008.10.005
  • Daum RS, Spellberg B. Progress toward a Staphylococcus aureus vaccine. Clin Infect Dis 2012; 54:560-7; PMID:22186773; http://dx.doi.org/10.1093/cid/cir828
  • Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, Yeoh H, Law D, Robbins JB, Schneerson R, et al. Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. N Engl J Med 2002; 346:491-6; PMID:11844850; http://dx.doi.org/10.1056/NEJMoa011297
  • Fattom A, Matalon A, Buerkert J, Taylor K, Damaso S, Boutriau D. Efficacy profile of a bivalent Staphylococcus aureus glycoconjugate vaccine in adults on hemodialysis: phase III randomized study. Hum Vaccin Immunother 2014; e34414.
  • Creech CB, 2nd Johnson BG, Alsentzer AR, Hohenboken M, Edwards KM, Talbot TR, 3rd. Vaccination as infection control: a pilot study to determine the impact of Staphylococcus aureus vaccination on nasal carriage. Vaccine 2009; 28:256-60; PMID:19799842; http://dx.doi.org/10.1016/j.vaccine.2009.09.088
  • Fowler VG, Allen KB, Moreira ED, Moustafa M, Isgro F, Boucher HW, Corey GR, Carmeli Y, Betts R, Hartzel JS, et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA 2013; 309:1368-78; PMID:23549582; http://dx.doi.org/10.1001/jama.2013.3010
  • Spellberg B, Daum R. A new view on development of a Staphylococcus aureus vaccine: insights from mice and men. Hum Vaccin 2010; 6:857-9; PMID:20930569; http://dx.doi.org/10.4161/hv.6.10.12469
  • Anderson AS, Miller AA, Donald RG, Scully IL, Nanra JS, Cooper D, Jansen KU. Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors. Hum Vaccin Immunother 2012; 8:1585-94; PMID:22922765; http://dx.doi.org/10.4161/hv.21872
  • Wacker M, Wang L, Kowarik M, Dowd M, Lipowsky G, Faridmoayer A, Shields K, Park S, Alaimo C, Kelley KA, et al. Prevention of Staphylococcus aureus infections by glycoprotein vaccines synthesized in Escherichia coli. J Infect Dis 2014; 209:1551-61; PMID:24308931; http://dx.doi.org/10.1093/infdis/jit800
  • Watts A, Ke D, Wang Q, Pillay A, Nicholson-Weller A, Lee JC. Staphylococcus aureus strains that express serotype 5 or serotype 8 capsular polysaccharides differ in virulence. Infect Immun 2005; 73:3502-11; PMID:15908379; http://dx.doi.org/10.1128/IAI.73.6.3502-3511.2005
  • Richmond P, Borrow R, Goldblatt D, Findlow J, Martin S, Morris R, Cartwright K, Miller E. Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers. J Infect Dis 2001; 183:160-3; PMID:11078484; http://dx.doi.org/10.1086/317646
  • Bhakdi S, Tranum-Jensen J. Alpha-toxin of Staphylococcus aureus. Microbiol Rev 1991; 55:733-51; PMID:1779933
  • Bubeck Wardenburg J, Schneewind O. Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med 2008; 205:287-94; PMID:18268041; http://dx.doi.org/10.1084/jem.20072208
  • Jarry TM, Memmi G, Cheung AL. The expression of alpha-haemolysin is required for Staphylococcus aureus phagosomal escape after internalization in CFT-1 cells. Cell Microbiol 2008; 10:1801-14; PMID:18466345; http://dx.doi.org/10.1111/j.1462-5822.2008.01166.x
  • Kubica M, Guzik K, Koziel J, Zarebski M, Richter W, Gajkowska B, Golda A, Maciag-Gudowska A, Brix K, Shaw L, et al. A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus phagocytosed by human monocyte-derived macrophages. PLoS One 2008; 3:e1409; PMID:18183290; http://dx.doi.org/10.1371/journal.pone.0001409
  • Loughman A, Fitzgerald JR, Brennan MP, Higgins J, Downer R, Cox D, Foster TJ. Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A. Mol Microbiol 2005; 57:804-18; PMID:16045623; http://dx.doi.org/10.1111/j.1365-2958.2005.04731.x
  • Brady RA, Mocca CP, Burns DL. Immunogenicity analysis of Staphylococcus aureus clumping factor A genetic variants. Clin Vaccine Immunol 2013; 20:1338-40; PMID:23803901; http://dx.doi.org/10.1128/CVI.00275-13
  • Adhikari RP, Ajao AO, Aman MJ, Karauzum H, Sarwar J, Lydecker AD, Johnson JK, Nguyen C, Chen WH, Roghmann MC. Lower antibody levels to Staphylococcus aureus exotoxins are associated with sepsis in hospitalized adults with invasive S. aureus infections. J Infect Dis 2012; 206:915-23; PMID:22807524; http://dx.doi.org/10.1093/infdis/jis462
  • Fritz SA, Tiemann KM, Hogan PG, Epplin EK, Rodriguez M, Al-Zubeidi DN, Bubeck Wardenburg J, Hunstad DA. A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection. Clin Infect Dis 2013; 56:1554-61; PMID:23446627; http://dx.doi.org/10.1093/cid/cit123
  • Adhikari RP, Karauzum H, Sarwar J, Abaandou L, Mahmoudieh M, Boroun AR, Vu H, Nguyen T, Devi VS, Shulenin S, et al. Novel structurally designed vaccine for S. aureus alpha-hemolysin: protection against bacteremia and pneumonia. PLoS One 2012; 7:e38567; PMID:22701668; http://dx.doi.org/10.1371/journal.pone.0038567
  • Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis 2010; 202:1050-8; PMID:20726702; http://dx.doi.org/10.1086/656043
  • Mocca CP, Brady RA, Burns DL. Role of Antibodies in Protection Elicited by Active Vaccination with Genetically Inactivated Alpha Hemolysin in a Mouse Model of Staphylococcus aureus Skin and Soft Tissue Infections. Clin Vaccine Immunol 2014; 21:622-7; PMID:24574539; http://dx.doi.org/10.1128/CVI.00051-14
  • Lattar SM, Noto Llana M, Denoel P, Germain S, Buzzola FR, Lee JC, Sordelli DO. Protein antigens increase the protective efficacy of a capsule-based vaccine against Staphylococcus aureus in a rat model of osteomyelitis. Infect Immun 2014; 82:83-91; PMID:24126523; http://dx.doi.org/10.1128/IAI.01050-13
  • Tuchscherr LP, Buzzola FR, Alvarez LP, Lee JC, Sordelli DO. Antibodies to capsular polysaccharide and clumping factor A prevent mastitis and the emergence of unencapsulated and small-colony variants of Staphylococcus aureus in mice. Infect Immun 2008; 76:5738-44; PMID:18809660; http://dx.doi.org/10.1128/IAI.00874-08
  • Gong R, Hu C, Xu H, Guo A, Chen H, Zhang G, Shi L. Evaluation of clumping factor A binding region A in a subunit vaccine against Staphylococcus aureus-induced mastitis in mice. Clin Vaccine Immunol 2010; 17:1746-52; PMID:20826613; http://dx.doi.org/10.1128/CVI.00162-10
  • Josefsson E, Higgins J, Foster TJ, Tarkowski A. Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence. PLoS One 2008; 3:e2206; http://dx.doi.org/10.1371/journal.pone.0002206
  • Narita K, Hu DL, Mori F, Wakabayashi K, Iwakura Y, Nakane A. Role of interleukin-17A in cell-mediated protection against Staphylococcus aureus infection in mice immunized with the fibrinogen-binding domain of clumping factor A. Infect Immun 2010; 78:4234-42; PMID:20679443; http://dx.doi.org/10.1128/IAI.00447-10
  • Dantes R, Mu Y, Belflower R, Aragon D, Dumyati G, Harrison LH, Lessa FC, Lynfield R, Nadle J, Petit S, et al. National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern Med 2013; 173:1970-8; PMID:24043270
  • Leroux-Roels I, Borkowski A, Vanwolleghem T, Drame M, Clement F, Hons E, Devaster JM, Leroux-Roels G. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007; 370:580-9; PMID:17707753; http://dx.doi.org/10.1016/S0140-6736(07)61297-5
  • Leroux-Roels I, Bernhard R, Gerard P, Drame M, Hanon E, Leroux-Roels G. Broad Clade 2 cross-reactive immunity induced by an adjuvanted clade 1 rH5N1 pandemic influenza vaccine. PLoS One 2008; 3:e1665; PMID:18301743; http://dx.doi.org/10.1371/journal.pone.0001665
  • Morel S, Didierlaurent A, Bourguignon P, Delhaye S, Baras B, Jacob V, Planty C, Elouahabi A, Harvengt P, Carlsen H, et al. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 2011; 29:2461-73; PMID:21256188; http://dx.doi.org/10.1016/j.vaccine.2011.01.011
  • Roman F, Clement F, Dewe W, Walravens K, Maes C, Willekens J, De Boever F, Hanon E, Leroux-Roels G. Effect on cellular and humoral immune responses of the AS03 adjuvant system in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials. Clin Vaccine Immunol 2011; 18:835-43; http://dx.doi.org/10.1128/CVI.00480-10
  • Berglund J, Vink P, Tavares Da Silva F, Lestrate P, Boutriau D. Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults. Clin Vaccine Immunol 2014; 21:56-65; PMID:24173029; http://dx.doi.org/10.1128/CVI.00430-13
  • Fattom AI, Horwith G, Fuller S, Propst M, Naso R. Development of StaphVAX, a polysaccharide conjugate vaccine against S. aureus infection: from the lab bench to phase III clinical trials. Vaccine 2004; 22:880-7; PMID:15040941; http://dx.doi.org/10.1016/j.vaccine.2003.11.034
  • Decker MD, Edwards KM, Bradley R, Palmer P. Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines. J Pediatr 1992; 120:184-9; PMID:1735812; http://dx.doi.org/10.1016/S0022-3476(05)80424-X
  • Croxtall JD, Dhillon S. Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix). Drugs 2012; 72:2407-30; PMID:23231026; http://dx.doi.org/10.2165/11209580-000000000-00000
  • Prymula R, Schuerman L. 10-valent pneumococcal nontypeable Haemophilus influenzae PD conjugate vaccine: Synflorix. Expert Rev Vaccines 2009; 8:1479-500; PMID:19863240; http://dx.doi.org/10.1586/erv.09.113
  • Langley JM, Frenette L, Ferguson L, Riff D, Sheldon E, Risi G, Johnson C, Li P, Kenney R, Innis B, et al. Safety and cross-reactive immunogenicity of candidate AS03-adjuvanted prepandemic H5N1 influenza vaccines: a randomized controlled phase 1/2 trial in adults. J Infect Dis 2010; 201:1644-53; PMID:20423222; http://dx.doi.org/10.1086/652701
  • McElhaney JE, Beran J, Devaster JM, Esen M, Launay O, Leroux-Roels G, Ruiz-Palacios GM, van Essen GA, Caplanusi A, Claeys C, et al. AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. Lancet Infect Dis 2013; 13:485-96; PMID:23518156; http://dx.doi.org/10.1016/S1473-3099(13)70046-X
  • Leroux-Roels G, Marchant A, Levy J, Van Damme P, Schwarz T, Horsmans Y, Kremsner P, Gabor J, Esen M, Carletti I, et al. Learnings from clinical assessment of innate responses induced by several adjuvants combined with HBsAg model antigen. Keystone Symp Immunol Mech Vaccin, Ottawa, Canada, 13 to 18 Dec 2012, P1045.
  • Fattom A, Schneerson R, Watson DC, Karakawa WW, Fitzgerald D, Pastan I, Li X, Shiloach J, Bryla DA, Robbins JB. Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A. Infect Immun 1993; 61:1023-32; PMID:8432585
  • Welch PG, Fattom A, Moore J, Jr., Schneerson R, Shiloach J, Bryla DA, Li X, Robbins JB. Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis. J Am Soc Nephrol 1996; 7:247-53; PMID:8785394
  • Landrum M, Lalani T, Niknian M, Maguire J, Hospenthal D, Fattom A, Taylor K, Fraser J, Wilkins K, Ellis M, et al. A Randomized, Multi-Center Trial to Evaluate the Safety and Immunogenicity of Staphylococcus aureus Toxoids, rAT and rLukS-PV, in Healthy Volunteers. IDSA Oct 21 2011, P718.
  • Richmond P, Nissen M, Marshall H, Shakib S, Hodsman P, Jiang Q, Rill D, Baber J, Eiden J, Jansen KU, et al. A randomised, placebo controlled phase 1 first-in-human study of a novel 3-antigen Staphylococcus aureus vaccine in healthy adults, poster LB2769. Proceedings of the 21st European Congress of Clinical Microbiology and Infectious diseases, 07 – 10 May 2011, Milan, Italy.
  • Frenck R, Buddy Creech C, Sheldon E, Seiden DJ, Kankam M, Baber J, Zito E, Hubler R, Eiden J, Severs JM, et al. Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (sa4ag) in healthy adults: results of a randomized, placebo-controlled first-in-human phase 1/2 study, ePoster 134. 24th European Congress of Clinical Microbiology and Infectious diseases, 10 – 13 May 2014, Barcelona, Spain.
  • Campbell JD, Edelman R, King JC, Jr., Papa T, Ryall R, Rennels MB. Safety, reactogenicity, and immunogenicity of a tetravalent meningococcal polysaccharide-diphtheria toxoid conjugate vaccine given to healthy adults. J Infect Dis 2002; 186:1848-51; PMID:12447774; http://dx.doi.org/10.1086/345763
  • Knuf M, Kowalzik F, Kieninger D. Comparative effects of carrier proteins on vaccine-induced immune response. Vaccine 2011; 29:4881-90; PMID:21549783; http://dx.doi.org/10.1016/j.vaccine.2011.04.053
  • Hawkins J, Kodali S, Matsuka YV, McNeil LK, Mininni T, Scully IL, Vernachio JH, Severina E, Girgenti D, Jansen KU, et al. A recombinant clumping factor A-containing vaccine induces functional antibodies to Staphylococcus aureus that are not observed after natural exposure. Clin Vaccine Immunol 2012; 19:1641-50; PMID:22896688; http://dx.doi.org/10.1128/CVI.00354-12
  • Lin L, Ibrahim AS, Xu X, Farber JM, Avanesian V, Baquir B, Fu Y, French SW, Edwards JE, Jr., Spellberg B. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog 2009; 5:e1000703; PMID:20041174; http://dx.doi.org/10.1371/journal.ppat.1000703
  • Minegishi Y, Karasuyama H. Defects in Jak-STAT-mediated cytokine signals cause hyper-IgE syndrome: lessons from a primary immunodeficiency. Int Immunol 2009; 21:105-12; PMID:19088064; http://dx.doi.org/10.1093/intimm/dxn134
  • Minegishi Y, Saito M. Molecular mechanisms of the immunological abnormalities in hyper-IgE syndrome. Ann N Y Acad Sci 2011; 1246:34-40; PMID:22236428; http://dx.doi.org/10.1111/j.1749-6632.2011.06280.x
  • Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, et al. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med 2009; 206:1291-301; PMID:19487419; http://dx.doi.org/10.1084/jem.20082767
  • de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, Feinberg J, von Bernuth H, Samarina A, Janniere L, et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med 2008; 205:1543-50; PMID:18591412; http://dx.doi.org/10.1084/jem.20080321
  • Senthilkumar A, Kumar S, Sheagren JN. Increased incidence of Staphylococcus aureus bacteremia in hospitalized patients with acquired immunodeficiency syndrome. Clin Infect Dis 2001; 33:1412-6; PMID:11565083; http://dx.doi.org/10.1086/322656
  • Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, Leung DY. Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol 2001; 116:658-63; PMID:11348452; http://dx.doi.org/10.1046/j.0022-202x.2001.01331.x
  • Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002; 347:1151-60; PMID:12374875; http://dx.doi.org/10.1056/NEJMoa021481
  • Harper EG, Guo C, Rizzo H, Lillis JV, Kurtz SE, Skorcheva I, Purdy D, Fitch E, Iordanov M, Blauvelt A. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 2009; 129:2175-83; PMID:19295614; http://dx.doi.org/10.1038/jid.2009.65
  • Hedrick MN, Lonsdorf AS, Shirakawa AK, Richard Lee CC, Liao F, Singh SP, Zhang HH, Grinberg A, Love PE, Hwang ST, et al. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest 2009; 119:2317-29
  • Niebuhr M, Gathmann M, Scharonow H, Mamerow D, Mommert S, Balaji H, Werfel T. Staphylococcal alpha-toxin is a strong inducer of interleukin-17 in humans. Infect Immun 2011; 79:1615-22; PMID:21245272; http://dx.doi.org/10.1128/IAI.00958-10
  • Breuer K, Wittmann M, Kempe K, Kapp A, Mai U, Dittrich-Breiholz O, Kracht M, Mrabet-Dahbi S, Werfel T. Alpha-toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis. Clin Exp Allergy 2005; 35:1088-95; PMID:16120092; http://dx.doi.org/10.1111/j.1365-2222.2005.02295.x
  • Moris P, van der Most R, Leroux-Roels I, Clement F, Drame M, Hanon E, Leroux-Roels GG, Van Mechelen M. H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol 2011; 31:443-54; PMID:21174144; http://dx.doi.org/10.1007/s10875-010-9490-6
  • Van Damme P, Kafeja F, Bambure V, Hanon E, Moris P, Roman F, Gillard P. Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18-60 years and older. Hum Vaccin Immunother 2013; 9:1512-22; PMID:23571166; http://dx.doi.org/10.4161/hv.24504
  • Rumke HC, Richardus JH, Rombo L, Pauksens K, Plassmann G, Durand C, Devaster JM, Dewe W, Oostvogels L. Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial. BMC Infect Dis 2013; 13:348; PMID:23890405; http://dx.doi.org/10.1186/1471-2334-13-348
  • Miller LS, Cho JS. Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol 2011; 11:505-18; PMID:21720387; http://dx.doi.org/10.1038/nri3010
  • Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 2010; 10:479-89; PMID:20559326
  • Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009; 27:485-517; PMID:19132915; http://dx.doi.org/10.1146/annurev.immunol.021908.132710
  • McNeela EA, Burke A, Neill DR, Baxter C, Fernandes VE, Ferreira D, Smeaton S, El-Rachkidy R, McLoughlin RM, Mori A, et al. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLoS Pathog 2010; 6:e1001191
  • Olliver M, Hiew J, Mellroth P, Henriques-Normark B, Bergman P. Human monocytes promote Th1 and Th17 responses to Streptococcus pneumoniae. Infect Immun 2011; 79:4210-7; PMID:21788380; http://dx.doi.org/10.1128/IAI.05286-11
  • Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, Monticelli S, Lanzavecchia A, Sallusto F. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta. Nature 2012; 484:514-8; PMID:22466287; http://dx.doi.org/10.1038/nature10957
  • Chlibek R, Bayas JM, Collins H, de la Pinta ML, Ledent E, Mols JF, Heineman TC. Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age. J Infect Dis 2013; 208:1953-61; PMID:23904292; http://dx.doi.org/10.1093/infdis/jit365
  • Montoya J, Solon JA, Cunanan SR, Acosta L, Bollaerts A, Moris P, Janssens M, Jongert E, Demoitie MA, Mettens P, et al. A randomized, controlled dose-finding Phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults. J Clin Immunol 2013; 33:1360-75; PMID:24142232
  • Vandepapeliere P, Horsmans Y, Moris P, Van Mechelen M, Janssens M, Koutsoukos M, Van Belle P, Clement F, Hanon E, Wettendorff M, et al. Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers. Vaccine 2008; 26:1375-86; PMID:18272264; http://dx.doi.org/10.1016/j.vaccine.2007.12.038
  • Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011; 332:974-7; PMID:21512004; http://dx.doi.org/10.1126/science.1206095
  • Schreiner J, Kretschmer D, Klenk J, Otto M, Buhring HJ, Stevanovic S, Wang JM, Beer-Hammer S, Peschel A, Autenrieth SE. Staphylococcus aureus phenol-soluble modulin peptides modulate dendritic cell functions and increase in vitro priming of regulatory T cells. J Immunol 2013; 190:3417-26; PMID:23460735; http://dx.doi.org/10.4049/jimmunol.1202563
  • Food and Drug A. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Available at: http://wwwfdagov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm091977pdf2007