One dose of staphylococcus aureus 4C-staph vaccine formulated with a novel TLR7-dependent adjuvant rapidly protects mice through antibodies, effector CD4+ T Cells, and IL-17A

PLoS ONE

Volumn 11, Issue 1, 2016, Pages

  Mancini, Francesca ^a,b,e   Monaci, Elisabetta ^a,e   Lofano, Giuseppe ^a,c,f   Torre, Antonina ^a   Bacconi, Marta ^a,d,e   Tavarini, Simona ^a,e   Sammicheli, Chiara ^a,e   Arcidiacono, Letizia ^a,e   Galletti, Bruno ^a,e   Laera, Donatello ^a,e   Pallaoro, Michele ^a,e   Tuscano, Giovanna ^a,e   Fontana, Maria Rita ^a,e   Bensi, Giuliano ^a,e   Grandi, Guido ^a,c,g   Rossi Paccani, Silvia ^a,e   Nuti, Sandra ^a,e   Rappuoli, Rino ^a,e   De Gregorio, Ennio ^a,e   Bagnoli, Fabio ^a,e   Soldaini, Elisabetta ^a,e   Bertholet, Sylvie ^a,e   more..

^a NOVARTIS VACCINES AND DIAGNOSTICS   (Italy)

^b UNIVERSITY OF PADOVA   (Italy)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

^d UNIVERSITY OF SIENA   (Italy)

^e GSK   (Italy)

^f MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^g UNIVERSITY OF TRENTO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA HEMOLYSIN; ALUMINUM POTASSIUM SULFATE; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; INTERLEUKIN 17; NEUTRALIZING ANTIBODY; STAPHYLOCOCCUS VACCINE; TOLL LIKE RECEPTOR 7; BACTERIUM ANTIBODY; CYTOKINE; IL17A PROTEIN, MOUSE; IMMUNOLOGICAL ADJUVANT;

ACTIVE IMMUNIZATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; BACTERIAL LOAD; BACTERIAL PERITONITIS; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; IN VIVO STUDY; KIDNEY ABSCESS; MOUSE; NONHUMAN; PASSIVE IMMUNIZATION; PERITONITIS; SINGLE DRUG DOSE; STAPHYLOCOCCUS INFECTION; TH1 CELL; TH17 CELL; ANIMAL; C57BL MOUSE; CYTOLOGY; GENETICS; IMMUNOLOGY; METABOLISM; MORTALITY; PATHOLOGY; SPLEEN; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; SURVIVAL RATE;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTIBODIES, BACTERIAL; ANTIBODIES, NEUTRALIZING; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; FEMALE; INTERLEUKIN-17; MICE; MICE, INBRED C57BL; SPLEEN; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCAL VACCINES; STAPHYLOCOCCUS AUREUS; SURVIVAL RATE; TH1 CELLS; TH17 CELLS; TOLL-LIKE RECEPTOR 7;

EID: 84958567984     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0147767     Document Type: Article

References (47)

1. Chen LF, Arduino JM, Sheng S, Muhlbaier LH, Kanafani ZA, Harris AD, et al. Epidemiology and outcome of major postoperative infections following cardiac surgery: Risk factors and impact of pathogen type. Am J Infect Control. 2012; 40(10):963-8. doi: 10.1016/j.ajic.2012.01.012 PMID: 22609237
2. Kanafani ZA, Arduino JM, Muhlbaier LH, Kaye KS, Allen KB, Carmeli Y, et al. Incidence of and preoperative risk factors for Staphylococcus aureus bacteremia and chest wound infection after cardiac surgery. Infect Control Hosp Epidemiol. 2009; 30(3):242-8. Epub 2009/02/10. doi: 10.1086/596015 PMID: 19199534.
3. Vincent J, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009; 302(21):2323-9. doi: 10.1001/jama. 2009.1754 PMID: 19952319
4. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012; 25(2):362-86. Epub 2012/04/12. doi: 10.1128/cmr.05022-11 PMID: 22491776; PubMed Central PMCID: PMCPmc3346297.
5. Bagnoli F, Fontana MR, Soldaini E, Mishra RPN, Fiaschi L, Cartocci E, et al. Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus. Proc Natl Acad Sci U S A. 2015. doi: 10.1073/pnas.1424924112
6. Menzies BE, Kernodle DS. Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: role of histidines in toxin activity in vitro and in a murine model. Infect Immun. 1994; 62 (5):1843-7. Epub 1994/05/01. PMID: 8168947; PubMed Central PMCID: PMCPmc186423.
7. Berube BJ, Bubeck Wardenburg J. Staphylococcus aureus alpha-toxin: nearly a century of intrigue. Toxins. 2013; 5(6):1140-66. Epub 2013/07/31. PMID: 23888516; PubMed Central PMCID: PMCPmc3717774.
8. Bubeck Wardenburg J, Schneewind O. Vaccine protection against Staphylococcus aureus pneumonia. J Exp Med. 2008; 205(2):287-94. Epub 2008/02/13. doi: 10.1084/jem.20072208 PMID: 18268041; PubMed Central PMCID: PMCPmc2271014.
9. Rauch S, DeDent AC, Kim HK, Bubeck Wardenburg J, Missiakas DM, Schneewind O. Abscess Formation and Alpha-Hemolysin Induced Toxicity in a Mouse Model of Staphylococcus aureus Peritoneal Infection. Infect Immun. 2012; 80(10):3721-32. doi: 10.1128/iai.00442-12 PMID: 22802349
10. Kennedy AD, Bubeck Wardenburg J, Gardner DJ, Long D, Whitney AR, Braughton KR, et al. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. J Infect Dis. 2010; 202(7):1050-8. Epub 2010/08/24. doi: 10.1086/656043 PMID: 20726702; PubMed Central PMCID: PMCPmc2945289.
11. Burts ML, Williams WA, DeBord K, Missiakas DM. EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections. Proc Natl Acad Sci U S A. 2005; 102(4):1169-74. doi: 10.1073/pnas.0405620102 PMID: 15657139
12. Korea CG, Balsamo G, Pezzicoli A, Merakou C, Tavarini S, Bagnoli F, et al. Staphylococcal Esx proteins modulate apoptosis and release of intracellular Staphylococcus aureus during infection in epithelial cells. Infect Immun. 2014; 82(10):4144-53. Epub 2014/07/23. doi: 10.1128/iai.01576-14 PMID: 25047846; PubMed Central PMCID: PMCPmc4187876.
13. Zhang BZ, Hua YH, Yu B, Lau CC, Cai JP, Zheng SY, et al. Recombinant ESAT-6-like proteins provoke protective immune responses against invasive Staphylococcus aureus disease in a murine model. Infect Immun. 2015; 83(1):339-45. Epub 2014/11/05. doi: 10.1128/iai.02498-14 PMID: 25368117; PubMed Central PMCID: PMCPmc4288882.
14. Mishra RPN, Mariotti P, Fiaschi L, Nosari S, Maccari S, Liberatori S, et al. Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. J Infect Dis. 2012; 206(7):1041-9. doi: 10.1093/infdis/jis463 PMID: 22829645
15. Mariotti P, Malito E, Biancucci M, Lo Surdo P, Mishra RP, Nardi-Dei V, et al. Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochem J. 2013; 449(3):683-93. Epub 2012/11/02. doi: 10.1042/bj20121426 PMID: 23113737.
16. Sebulsky MT, Heinrichs DE. Identification and characterization of fhuD1 and fhuD2, two genes involved in iron-hydroxamate uptake in Staphylococcus aureus. J Bacteriol. 2001; 183(17):4994-5000. Epub 2001/08/08. PMID: 11489851; PubMed Central PMCID: PMC95374.
17. Schluepen C, Malito E, Marongiu A, Schirle M, McWhinnie E, Lo Surdo P, et al. Mining the bacterial unknown proteome: identification and characterization of a novel family of highly conserved protective antigens in Staphylococcus aureus. Biochem J. 2013; 455(3):273-84. Epub 2013/07/31. doi: 10.1042/bj20130540 PMID: 23895222.
18. Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013; 19(12):1597-608. Epub 2013/12/07. doi: 10.1038/nm.3409 PMID: 24309663.
19. Maisonneuve C, Bertholet S, Philpott DJ, De Gregorio E. Unleashing the potential of NOD-and Toll-like agonists as vaccine adjuvants. Proc Natl Acad Sci U S A. 2014; 111(34):12294-9. Epub 2014/08/20. doi: 10.1073/pnas.1400478111 PMID: 25136133; PubMed Central PMCID: PMCPmc4151741.
20. Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015; 135(3):626-35. Epub 2014/12/22. doi: 10.1016/j.jaci. 2014.11.001 PMID: 25528359.
21. Medzhitov R, Janeway CA Jr. Innate Immunity: The Virtues of a Nonclonal System of Recognition. Cell. 1997; 91(3):295-8. doi: 10.1016/S0092-8674(00)80412-2 PMID: 9363937
22. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004; 4(7):499-511. Epub 2004/07/02. doi: 10.1038/nri1391 PMID: 15229469.
23. Vasilakos JP, Tomai MA. The use of Toll-like receptor 7/8 agonists as vaccine adjuvants. Expert Rev Vaccines. 2013; 12(7):809-19. doi: 10.1586/14760584.2013.811208 PMID: 23885825
24. Wu TY, Singh M, Miller AT, De Gregorio E, Doro F, D'Oro U, et al. Rational design of small molecules as vaccine adjuvants. Sci Transl Med. 2014; 6(263):263ra160. Epub 2014/11/21. doi: 10.1126/scitranslmed.3009980 PMID: 25411473.
25. Chen J, Trounstine M, Alt FW, Young F, Kurahara C, Loring JF, et al. Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol. 1993; 5 (6):647-56. Epub 1993/06/01. PMID: 8347558.
26. Pozzi C, Lofano G, Mancini F, Soldaini E, Speziale P, De Gregorio E, et al. Phagocyte subsets and lymphocyte clonal deletion behind ineffective immune response to Staphylococcus aureus. FEMS Microbiol Rev. 2015. Epub 2015/05/23. doi: 10.1093/femsre/fuv024 PMID: 25994610.
27. Proctor RA. Challenges for a universal Staphylococcus aureus vaccine. Clin Infect Dis. 2012; 54 (8):1179-86. Epub 2012/02/23. doi: 10.1093/cid/cis033 PMID: 22354924.
28. Maurer K, Reyes-Robles T, Alonzo F 3rd, Durbin J, Torres VJ, Cadwell K. Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin. Cell Host Microbe. 2015; 17(4):429-40. Epub 2015/03/31. doi: 10.1016/j.chom.2015.03.001 PMID: 25816775; PubMed Central PMCID: PMCPmc4392646.
29. Kim HK, DeDent A, Cheng AG, McAdow M, Bagnoli F, Missiakas DM, et al. IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine. 2010; 28(38):6382-92. Epub 2010/03/17. doi: 10.1016/j.vaccine.2010.02.097 PMID: 20226248; PubMed Central PMCID: PMCPmc3095377.
30. Fattom A, Matalon A, Buerkert J, Taylor K, Damaso S, Boutriau D. Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study. Hum Vaccin Immunother. 2015; 11(3):632-41. Epub 2014/12/09. doi: 10.4161/hv.34414 PMID: 25483694.
31. Cypowyj S, Picard C, Marodi L, Casanova JL, Puel A. Immunity to infection in IL-17-deficient mice and humans. Eur J Immunol. 2012; 42(9):2246-54. Epub 2012/09/06. doi: 10.1002/eji.201242605 PMID: 22949323; PubMed Central PMCID: PMCPmc3720135.
32. Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL, et al. Primary immunodeficiencies underlying fungal infections. Curr Opin Pediatr. 2013; 25(6):736-47. Epub 2013/11/19. doi: 10.1097/mop.0000000000000031 PMID: 24240293; PubMed Central PMCID: PMCPmc4098727.
33. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014; 14(9):585-600. Epub 2014/08/26. doi: 10.1038/nri3707 PMID: 25145755; PubMed Central PMCID: PMCPmc4281037.
34. Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001; 194(4):519-27. Epub 2001/08/22. PMID: 11514607; PubMed Central PMCID: PMCPmc2193502.
35. Meller S, Di Domizio J, Voo KS, Friedrich HC, Chamilos G, Ganguly D, et al. TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol. 2015; 16(9):970-9. Epub 2015/07/15. doi: 10.1038/ni.3211 PMID: 26168081.
36. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest. 2010; 120(5):1762-73. Epub 2010/04/07. doi: 10.1172/jci40891 PMID: 20364087; PubMed Central PMCID: PMC2860944.
37. Cheng AG, Kim HK, Burts ML, Krausz T, Schneewind O, Missiakas DM. Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J. 2009; 23 (10):3393-404. doi: 10.1096/fj.09-135467 PMID: 19525403
38. Maher BM, Mulcahy ME, Murphy AG, Wilk M, O'Keeffe KM, Geoghegan JA, et al. Nlrp-3-driven interleukin 17 production by gammadeltaT cells controls infection outcomes during Staphylococcus aureus surgical site infection. Infect Immun. 2013; 81(12):4478-89. Epub 2013/10/02. doi: 10.1128/iai.01026-13 PMID: 24082072; PubMed Central PMCID: PMCPmc3837970.
39. Murphy AG, O'Keeffe KM, Lalor SJ, Maher BM, Mills KH, McLoughlin RM. Staphylococcus aureus infection of mice expands a population of memory gammadelta T cells that are protective against subsequent infection. J Immunol. 2014; 192(8):3697-708. Epub 2014/03/14. doi: 10.4049/jimmunol. 1303420 PMID: 24623128; PubMed Central PMCID: PMCPmc3979672.
40. Joshi A, Pancari G, Cope L, Bowman EP, Cua D, Proctor RA, et al. Immunization with Staphylococcus aureus iron regulated surface determinant B (IsdB) confers protection via Th17/IL17 pathway in a murine sepsis model. Hum Vaccin Immunother. 2012; 8(3):336-46. doi: 10.4161/hv.18946 PMID: 22327491
41. Lin L, Ibrahim AS, Xu X, Farber JM, Avanesian V, Baquir B, et al. Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice. PLoS Pathog. 2009; 5(12):e1000703. doi: 10.1371/journal.ppat.1000703 PMID: 20041174
42. Narita K, Hu D-L, 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(10):4234-42. doi: 10.1128/iai.00447-10 PMID: 20679443
43. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, et al. Differential roles of interleukin-17A and-17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009; 30(1):108-19. Epub 2009/01/16. doi: 10.1016/j.immuni.2008.11.009 PMID: 19144317.
44. Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-wit D, et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol. 2007; 8(3):247-56. doi: http://www.nature.com/ni/journal/v8/n3/suppinfo/ni1439-S1.html. PMID: 17277779
45. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009; 9(8):556-67. doi: 10.1038/nri2586 PMID: 19575028
46. van Kessel KP, Bestebroer J, van Strijp JA. Neutrophil-Mediated Phagocytosis of Staphylococcus aureus. Front Immunol. 2014; 5:467. Epub 2014/10/14. doi: 10.3389/fimmu.2014.00467 PMID: 25309547; PubMed Central PMCID: PMCPmc4176147.
47. von Köckritz-Blickwede M, Rohde M, Oehmcke S, Miller LS, Cheung AL, Herwald H, et al. Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. Am J Pathol. 2008; 173(6):1657-68. doi: 10.2353/ajpath.2008.080337 PMID: 18974303