Outer membrane vesicles: moving within the intricate labyrinth of assays that can predict risks of reactogenicity in humans

References

• Kuehn MJ. Bacterial outer membrane vesicles and the host-pathogen interaction. Genes Dev. 2005;19(22):2645–55. doi:10.1101/gad.1299905.
   PubMed Web of Science ®Google Scholar
• van der Pol L, Stork M, van der Ley P. Outer membrane vesicles as platform vaccine technology. Biotechnol J. 2015;10(11):1689–706. doi:10.1002/biot.201400395.
   PubMed Web of Science ®Google Scholar
• Bishop DG, Work E. An extracellular glycolipid produced by Escherichia coli grown under lysine-limiting conditions. Biochem J. 1965;96(2):567–76. doi:10.1042/bj0960567.
   PubMed Web of Science ®Google Scholar
• Berlanda Scorza F, Colucci AM, Maggiore L, Sanzone S, Rossi O, Ferlenghi I, Pesce I, Caboni M, Norais N, Di Cioccio V, et al. High yield production process for Shigella outer membrane particles. PLoS One. 2012;7(6):e35616. doi:10.1371/journal.pone.0035616.
   PubMed Web of Science ®Google Scholar
• Necchi F, Saul A, Rondini S. Development of a high-throughput method to evaluate serum bactericidal activity using bacterial ATP measurement as survival readout. PLoS One. 2017;12(2):e0172163. doi:10.1371/journal.pone.0172163.
   PubMed Web of Science ®Google Scholar
• Baker SM, Davitt CJH, Motyka N, Kikendall NL, Russell-Lodrigue K, Roy CJ, Morici LA. A burkholderia pseudomallei outer membrane vesicle vaccine provides cross protection against inhalational glanders in mice and non-human primates. Vaccines (Basel). 2017;5(4):49
   PubMed Web of Science ®Google Scholar
• Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D, Dull P, Kimura A. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet. 2013;381(9869):825–35. doi:10.1016/S0140-6736(12)61961-8.
   PubMed Web of Science ®Google Scholar
• Keiser PB, Biggs-Cicatelli S, Moran EE, Schmiel DH, Pinto VB, Burden RE, Miller LB, Moon JE, Bowden RA, Cummings JF, et al. A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression. Vaccine. 2011;29(7):1413–20. doi:10.1016/j.vaccine.2010.12.039.
   PubMed Web of Science ®Google Scholar
• Rappuoli R, Pizza M, Masignani V, Vadivelu K. Meningococcal B vaccine (4CMenB): the journey from research to real world experience. Expert Rev Vaccines. 2018;17(12):1111–21. doi:10.1080/14760584.2018.1547637.
   PubMed Web of Science ®Google Scholar
• Micoli F, Rondini S, Alfini R, Lanzilao L, Necchi F, Negrea A, Rossi O, Brandt C, Clare S, Mastroeni P, et al. Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella. Proc Natl Acad Sci U S A. 2018;115(41):10428–33. doi:10.1073/pnas.1807655115.
   PubMed Web of Science ®Google Scholar
• Sanders H, Feavers IM. Adjuvant properties of meningococcal outer membrane vesicles and the use of adjuvants in Neisseria meningitidis protein vaccines. Expert Rev Vaccines. 2011;10(3):323–34. doi:10.1586/erv.11.10.
   PubMed Web of Science ®Google Scholar
• Alaniz RC, Deatherage BL, Lara JC, Cookson BT. Membrane vesicles are immunogenic facsimiles of salmonella typhimurium that potently activate dendritic cells, prime B and T cell responses, and stimulate protective immunity in vivo. J Immunol. 2007;179(11):7692–701. doi:10.4049/jimmunol.179.11.7692.
   PubMed Web of Science ®Google Scholar
• Gerke C, Colucci AM, Giannelli C, Sanzone S, Vitali CG, Sollai L, Rossi O, Martin LB, Auerbach J, Di Cioccio V, et al. Production of a Shigella sonnei vaccine based on generalized modules for membrane antigens (GMMA), 1790GAHB. PLoS One. 2015;10(8):e0134478. doi:10.1371/journal.pone.0134478.
   PubMed Web of Science ®Google Scholar
• Rossi O, Caboni M, Negrea A, Necchi F, Alfini R, Micoli F, Saul A, MacLennan CA, Rondini S, Gerke C, et al. Toll-like receptor activation by generalized modules for membrane antigens from lipid A mutants of Salmonella enterica serovars typhimurium and enteritidis. Clin Vaccine Immunol. 2016;23(4):304–14. doi:10.1128/CVI.00023-16.
   PubMed Web of Science ®Google Scholar
• Rossi O, Pesce I, Giannelli C, Aprea S, Caboni M, Citiulo F, Valentini S, Ferlenghi I, MacLennan CA, D'Oro U, et al. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications. J Biol Chem. 2014;289(36):24922–35. doi:10.1074/jbc.M114.566570.
   PubMed Web of Science ®Google Scholar
• Koeberling O, Ispasanie E, Hauser J, Rossi O, Pluschke G, Caugant DA, Saul A, MacLennan CA. A broadly-protective vaccine against meningococcal disease in sub-Saharan Africa based on generalized modules for membrane antigens (GMMA). Vaccine. 2014;32(23):2688–95. doi:10.1016/j.vaccine.2014.03.068.
   PubMed Web of Science ®Google Scholar
• Gnopo YMD, Watkins HC, Stevenson TC, DeLisa MP, Putnam D. Designer outer membrane vesicles as immunomodulatory systems – reprogramming bacteria for vaccine delivery. Adv Drug Deliv Rev. 2017;114:132–42. doi:10.1016/j.addr.2017.05.003.
   PubMed Web of Science ®Google Scholar
• Stevenson TC, Cywes-Bentley C, Moeller TD, Weyant KB, Putnam D, Chang YF, Jones BD, Pier GB, DeLisa MP. Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies. Proc Natl Acad Sci U S A. 2018;115(14):E3106–E15. doi:10.1073/pnas.1718341115.
   PubMed Web of Science ®Google Scholar
• Koeberling O, Giuntini S, Seubert A, Granoff DM. Meningococcal outer membrane vesicle vaccines derived from mutant strains engineered to express factor H binding proteins from antigenic variant groups 1 and 2. Clin Vaccine Immunol. 2009;16(2):156–62. doi:10.1128/CVI.00403-08.
   PubMedGoogle Scholar
• Watkins HC, Rappazzo CG, Higgins JS, Sun X, Brock N, Chau A, Misra A, Cannizzo JPB, King MR, Maines TR, et al. Safe recombinant outer membrane vesicles that display M2e elicit heterologous influenza protection. Molecular Therapy. 2017;25(4):989–1002. doi:10.1016/j.ymthe.2017.01.010.
   PubMed Web of Science ®Google Scholar
• Scaria PV, Rowe CG, Chen BB, Muratova OV, Fischer ER, Barnafo EK, Anderson CF, Zaidi IU, Lambert LE, Lucas BJ, et al. Outer membrane protein complex as a carrier for malaria transmission blocking antigen Pfs230. NPJ Vaccines. 2019;4(1):24. doi:10.1038/s41541-019-0121-9.
   PubMed Web of Science ®Google Scholar
• Grandi A, Tomasi M, Zanella I, Ganfini L, Caproni E, Fantappie L, Irene C, Frattini L, Isaac SJ, König E, et al. Synergistic protective activity of tumor-specific epitopes engineered in bacterial outer membrane vesicles. Front Oncol. 2017;7:253. doi:10.3389/fonc.2017.00253.
   PubMed Web of Science ®Google Scholar
• Ferrari G, Garaguso I, Adu-Bobie J, Doro F, Taddei AR, Biolchi A, Brunelli B, Giuliani MM, Pizza M, Norais N, et al. Outer membrane vesicles from group B Neisseria meningitidis delta gna33 mutant: proteomic and immunological comparison with detergent-derived outer membrane vesicles. Proteomics. 2006;6(6):1856–66. doi:10.1002/pmic.200500164.
   PubMed Web of Science ®Google Scholar
• De Benedetto G, Alfini R, Cescutti P, Caboni M, Lanzilao L, Necchi F, Saul A, MacLennan CA, Rondini S, Micoli F, et al. Characterization of O-antigen delivered by Generalized Modules for membrane antigens (GMMA) vaccine candidates against nontyphoidal Salmonella. Vaccine. 2017;35(3):419–26. doi:10.1016/j.vaccine.2016.11.089.
   PubMed Web of Science ®Google Scholar
• van de Waterbeemd B, Streefland M, van der Ley P, Zomer B, van Dijken H, Martens D, Wijffels R, van der Pol L. Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process. Vaccine. 2010;28(30):4810–16. doi:10.1016/j.vaccine.2010.04.082.
   PubMed Web of Science ®Google Scholar
• van de Waterbeemd B, Zomer G, Kaaijk P, Ruiterkamp N, Wijffels RH, van den Dobbelsteen GP, van der Pol LA. Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis. PLoS One. 2013;8(5):e65157. doi:10.1371/journal.pone.0065157.
   PubMed Web of Science ®Google Scholar
• Mahla RS, Reddy MC, Prasad DV, Kumar H. Sweeten PAMPs: role of sugar complexed PAMPs in innate immunity and vaccine biology. Front Immunol. 2013;4:248. doi:10.3389/fimmu.2013.00248.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84. doi:10.1038/ni.1863.
   PubMed Web of Science ®Google Scholar
• Bishop RE. Polymorphic regulation of outer membrane lipid A composition. mBio. 2016;7(6). doi:10.1128/mBio.01903-16.
   Web of Science ®Google Scholar
• De Gregorio E, Caproni E, Ulmer JB. Vaccine adjuvants: mode of action. Front Immunol. 2013;4:214. doi:10.3389/fimmu.2013.00214.
   PubMed Web of Science ®Google Scholar
• Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, Ulmer AJ, Zähringer U, Seydel U, Di Padova F, et al. Bacterial endotoxin: molecular relationships of structure to activity and function. Faseb J. 1994;8(2):217–25. doi:10.1096/fasebj.8.2.8119492.
   PubMed Web of Science ®Google Scholar
• Schromm AB, Brandenburg K, Loppnow H, Moran AP, Koch MH, Rietschel ET, Seydel U. Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion. Eur J Biochem. 2000;267(7):2008–13. doi:10.1046/j.1432-1327.2000.01204.x.
   PubMedGoogle Scholar
• Seydel U, Oikawa M, Fukase K, Kusumoto S, Brandenburg K. Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity. Eur J Biochem. 2000;267(10):3032–39. doi:10.1046/j.1432-1033.2000.01326.x.
   PubMedGoogle Scholar
• Raetz CR, Guan Z, Ingram BO, Six DA, Song F, Wang X, Zhao J. Discovery of new biosynthetic pathways: the lipid A story. J Lipid Res. 2009;50(Suppl):S103–8. doi:10.1194/jlr.R800060-JLR200.
   PubMedGoogle Scholar
• Raetz CR, Reynolds CM, Trent MS, Bishop RE. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem. 2007;76(1):295–329. doi:10.1146/annurev.biochem.76.010307.145803.
   PubMedGoogle Scholar
• Matsuura M. Structural modifications of bacterial lipopolysaccharide that facilitate gram-negative bacteria evasion of host innate immunity. Front Immunol. 2013;4:109. doi:10.3389/fimmu.2013.00109.
   PubMed Web of Science ®Google Scholar
• Trent MS, Stead CM, Tran AX, Hankins JV. Diversity of endotoxin and its impact on pathogenesis. J Endotoxin Res. 2006;12(4):205–23. doi:10.1179/096805106X118825.
   PubMedGoogle Scholar
• Rebeil R, Ernst RK, Jarrett CO, Adams KN, Miller SI, Hinnebusch BJ. Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation. J Bacteriol. 2006;188(4):1381–88. doi:10.1128/JB.188.4.1381-1388.2006.
   PubMed Web of Science ®Google Scholar
• Hajjar AM, Harvey MD, Shaffer SA, Goodlett DR, Sjostedt A, Edebro H, Forsman M, Bystrom M, Pelletier M, Wilson CB, et al. Lack of in vitro and in vivo recognition of Francisella tularensis subspecies lipopolysaccharide by Toll-like receptors. Infect Immun. 2006;74:6730–38.
   PubMed Web of Science ®Google Scholar
• Zariri A, van der Ley P. Biosynthetically engineered lipopolysaccharide as vaccine adjuvant. Expert Rev Vaccines. 2015;14(6):861–76. doi:10.1586/14760584.2015.1026808.
   PubMed Web of Science ®Google Scholar
• Asensio CJ, Gaillard ME, Moreno G, Bottero D, Zurita E, Rumbo M, van der Ley P, van der Ark A, Hozbor D. Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid a deacylase PagL as a novel acellular vaccine candidate. Vaccine. 2011;29(8):1649–56. doi:10.1016/j.vaccine.2010.12.068.
   PubMed Web of Science ®Google Scholar
• Isitt C, Cosgrove CA, Ramsay ME, Ladhani SN. Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience. Arch Dis Child. 2020. doi:10.1136/archdischild-2019-318047.
   PubMed Web of Science ®Google Scholar
• Keiser PB, Gibbs BT, Coster TS, Moran EE, Stoddard MB, Labrie JE 3rd, Schmiel DH, Pinto V, Chen P, Zollinger WD, et al. A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA. Vaccine. 2010;28(43):6970–76. doi:10.1016/j.vaccine.2010.08.048.
   PubMed Web of Science ®Google Scholar
• Launay O, Lewis DJM, Anemona A, Loulergue P, Leahy J, Scire AS, Maugard A, Marchetti E, Zancan S, Huo Z, et al. Safety profile and immunologic responses of a novel vaccine against Shigella sonnei administered intramuscularly, intradermally and intranasally: results from two parallel randomized Phase 1 clinical studies in healthy adult volunteers in Europe. EBioMedicine. 2017;22:164–72. doi:10.1016/j.ebiom.2017.07.013.
   PubMed Web of Science ®Google Scholar
• Leitner DR, Lichtenegger S, Temel P, Zingl FG, Ratzberger D, Roier S, Schild-Prüfert K, Feichter S, Reidl J, Schild S, et al. A combined vaccine approach against Vibrio cholerae and ETEC based on outer membrane vesicles. Front Microbiol. 2015;6:823. doi:10.3389/fmicb.2015.00823.
   PubMed Web of Science ®Google Scholar
• Needham BD, Carroll SM, Giles DK, Georgiou G, Whiteley M, Trent MS. Modulating the innate immune response by combinatorial engineering of endotoxin. Proc Natl Acad Sci U S A. 2013;110(4):1464–69. doi:10.1073/pnas.1218080110.
   PubMed Web of Science ®Google Scholar
• Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009;458(7242):1191–95. doi:10.1038/nature07830.
   PubMed Web of Science ®Google Scholar
• Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. 2014;5:316. doi:10.3389/fimmu.2014.00316.
   PubMed Web of Science ®Google Scholar
• Noreen M, Shah MA, Mall SM, Choudhary S, Hussain T, Ahmed I, Jalil SF, Raza MI. TLR4 polymorphisms and disease susceptibility. Inflamm Res. 2012;61(3):177–88. doi:10.1007/s00011-011-0427-1.
   PubMed Web of Science ®Google Scholar
• Li YP, Yu SL, Huang ZJ, Huang J, Pan J, Feng X, Zhang XG, Wang JH, Wang J. An impaired inflammatory cytokine response to gram-negative LPS in human neonates is associated with the defective TLR-mediated signaling pathway. J Clin Immunol. 2015;35(2):218–26. doi:10.1007/s10875-015-0128-6.
   PubMed Web of Science ®Google Scholar
• Neun BW, Dobrovolskaia MA. Detection and quantitative evaluation of endotoxin contamination in nanoparticle formulations by LAL-based assays. Methods Mol Biol. 2011;697:121–30.
   PubMedGoogle Scholar
• Fisseha M, Chen P, Brandt B, Kijek T, Moran E, Zollinger W. Characterization of native outer membrane vesicles from lpxL mutant strains of Neisseria meningitidis for use in parenteral vaccination. Infect Immun. 2005;73(7):4070–80. doi:10.1128/IAI.73.7.4070-4080.2005.
   PubMed Web of Science ®Google Scholar
• European Pharmacopeia 9.0. 9th edition Council of Europe, Strasburg, France. Chapter 2.6.14. Bacterial Endotoxin, 2017. p. 204–207.
   Google Scholar
• Greisman SE, Hornick RB. Comparative pyrogenic reactivity of rabbit and man to bacterial endotoxin. Proc Soc Exp Biol Med. 1969;131(4):1154–58. doi:10.3181/00379727-131-34059.
   PubMed Web of Science ®Google Scholar
• Obiero CW, Ndiaye AGW, Scire AS, Kaunyangi BM, Marchetti E, Gone AM, Schütte LD, Riccucci D, Auerbach J, Saul A, et al. A Phase 2a randomized study to evaluate the safety and immunogenicity of the 1790GAHB generalized modules for membrane antigen vaccine against Shigella sonnei administered intramuscularly to adults from a shigellosis-endemic country. Front Immunol. 2017;8:1884. doi:10.3389/fimmu.2017.01884.
   PubMed Web of Science ®Google Scholar
• Norheim G, Sanders H, Mellesdal JW, Sundfor I, Chan H, Brehony C, Vipond C, Dold C, Care R, Saleem M, et al. An OMV vaccine derived from a capsular group b meningococcus with constitutive FetA Expression: preclinical evaluation of immunogenicity and toxicity. PLoS One. 2015;10(9):e0134353. doi:10.1371/journal.pone.0134353.
   PubMed Web of Science ®Google Scholar
• Marsay L, Dold C, Green CA, Rollier CS, Norheim G, Sadarangani M, Shanyinde M, Brehony C, Thompson AJ, Sanders H, et al. A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: a phase I clinical trial. J Infect. 2015;71(3):326–37. doi:10.1016/j.jinf.2015.05.006.
   PubMed Web of Science ®Google Scholar
• [accessed 2012 Nov 15]. https://wwwemaeuropaeu/en/documents/assessment-report/bexsero-epar-public-assessment-report_enpdf.
   Google Scholar
• Zbinden G. The concept of multispecies testing in industrial toxicology. Regul Toxicol Pharmacol. 1993;17(1):85–94. doi:10.1006/rtph.1993.1009.
   PubMed Web of Science ®Google Scholar
• Baldrick P. Safety evaluation to support first-in-man investigations II: toxicology studies. Regul Toxicol Pharmacol. 2008;51(2):237–43. doi:10.1016/j.yrtph.2008.04.006.
   PubMed Web of Science ®Google Scholar
• Monticello TM, Jones TW, Dambach DM, Potter DM, Bolt MW, Liu M, Keller DA, Hart TK, Kadambi VJ. Current nonclinical testing paradigm enables safe entry to first-in-human clinical trials: the IQ consortium nonclinical to clinical translational database. Toxicol Appl Pharmacol. 2017;334:100–09. doi:10.1016/j.taap.2017.09.006.
   PubMed Web of Science ®Google Scholar
• Shanks N, Greek R, Greek J. Are animal models predictive for humans? Philos Ethics Humanit Med. 2009;4(1):2. doi:10.1186/1747-5341-4-2.
   PubMedGoogle Scholar
• Zafack JG, Bureau A, Skowronski DM, De Serres G. Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials. BMJ Open. 2019;9(5):e026953. doi:10.1136/bmjopen-2018-026953.
   PubMed Web of Science ®Google Scholar
• Sheerin D, O’Connor D, Dold C, Clutterbuck E, Attar M, Rollier CS, Sadarangani M, Pollard AJ. Comparative transcriptomics between species attributes reactogenicity pathways induced by the capsular group B meningococcal vaccine, 4CMenB, to the membrane-bound endotoxin of its outer membrane vesicle component. Sci Rep. 2019;9(1):13797. doi:10.1038/s41598-019-50310-0.
   PubMedGoogle Scholar
• European Pharmacopeia 9.0. 9th edition Council of Europe, Strasburg, France. Chapter 2.6.8.. Pyrogens. 2017. p. 193–194. .
   Google Scholar
• Hull D, Vinter J, McIntyre J. The effect of endotoxin-induced fever on thermoregulation in the newborn rabbit. J Physiol. 1993;461(1):75–84. doi:10.1113/jphysiol.1993.sp019502.
   PubMedGoogle Scholar
• van Dijck P, van de Voorde H. Factors affecting pyrogen testing in rabbits. Dev Biol Stand. 1977;34:57–63.
   PubMedGoogle Scholar
• Bellentani L. Cyclic and chronobiological considerations when employing the rabbit fever test. Prog Clin Biol Res. 1982;93:329–42.
   PubMedGoogle Scholar
• Frasch CE, van Alphen L, Holst J, Poolman JT, Rosenqvist E. Outer membrane protein vesicle vaccines for meningococcal disease. Methods Mol Med. 2001;66:81–107. doi:10.1385/1-59259-148-5:81.
   PubMedGoogle Scholar
• Medsafe. Full Consent Application for the Meningococcal GroupB OMV vaccine MeNZB, by Chiron at the Rosia and Siena Sites, Italy Application in Accordance with Medicines Act 1981 and Medicines Regulations 1984, for Consent to distribute in New Zealand 2006.
   Google Scholar
• Vipond C, Findlay L, Feavers I, Care R. Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines. Altex. 2016;33:47–53. doi:10.14573/altex.1509291.
   PubMedGoogle Scholar
• Kaaijk P, van Straaten I, van de Waterbeemd B, Boot EP, Levels LM, van Dijken HH, van den Dobbelsteen GPJM. Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease. Vaccine. 2013;31(7):1065–71. doi:10.1016/j.vaccine.2012.12.031.
   PubMed Web of Science ®Google Scholar
• Raeven RHM, Brummelman J, Pennings JLA, van der Maas L, Helm K, Tilstra W, van der Ark A, Sloots A, van der Ley P, van Eden W, et al. Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination. Mucosal Immunol. 2018;11(3):1009. doi:10.1038/mi.2017.110.
   PubMed Web of Science ®Google Scholar
• Kaaijk P, van der Ark AA, van Amerongen G, van den Dobbelsteen GP. Nonclinical vaccine safety evaluation: advantages of continuous temperature monitoring using abdominally implanted data loggers. J Appl Toxicol. 2013;33(6):521–26. doi:10.1002/jat.2720.
   PubMed Web of Science ®Google Scholar
• Rosenqvist E, Hoiby EA, Bjune G, Aase A, Halstensen A, Lehmann AK, Paulssen J, Holst J, Michaelsen TE, Nøkleby H, et al. Effect of aluminium hydroxide and meningococcal serogroup C capsular polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria meningitidis outer membrane vesicle vaccine. Dev Biol Stand. 1998;92:323–33.
   PubMedGoogle Scholar
• Shoemaker DR, Saunders NB, Brandt BL, Moran EE, Laclair AD, Zollinger WD. Intranasal delivery of group B meningococcal native outer membrane vesicle vaccine induces local mucosal and serum bactericidal antibody responses in rabbits. Infect Immun. 2005;73(8):5031–38. doi:10.1128/IAI.73.8.5031-5038.2005.
   PubMed Web of Science ®Google Scholar
• Adriani R, Mousavi Gargari SL, Nazarian S, Sarvary S, Noroozi N. Immunogenicity of Vibrio cholerae outer membrane vesicles secreted at various environmental conditions. Vaccine. 2018;36(2):322–30. doi:10.1016/j.vaccine.2017.09.004.
   PubMed Web of Science ®Google Scholar
• European Pharmacopeia 9.0. 9th edition Council of Europe, Strasburg, France. Chapter 2.6.30. Monocyte activation test.
   Google Scholar
• Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes Text with EEA relevance. Strasburg, France.Document 32010L0063. 2010. p. 33–79.
   Google Scholar
• Netea MG, Kullberg BJ, Van der Meer JW. Circulating cytokines as mediators of fever. Clinical Infectious Diseases. 2000;31(Suppl 5):S178–84. doi:10.1086/317513.
   PubMed Web of Science ®Google Scholar
• Valentini S, Santoro G, Baffetta F, Franceschi S, Paludi M, Brandini E, Gherardini L, SerruD, Capecchi B. Monocyte-activation test to reliably measure the pyrogenic content of a vaccine: an in vitro pyrogen test to overcome in vivo limitations. Vaccine 37(2019):3754–3760.
   Web of Science ®Google Scholar
• Vipond C, Sutherland J, Nordgren K, Kemp G, Heath A, Care R, Studholme L. Development and validation of a monocyte activation test for the control/safety testing of an OMV-based meningococcal B vaccine. Vaccine. 2019;37(29):3747–53. doi:10.1016/j.vaccine.2018.06.038.
   PubMed Web of Science ®Google Scholar
• Studholme L, Sutherland J, Desai T, Hockley J, Care R, IK N, Vipond C. Evaluation of the monocyte activation test for the safety testing of meningococcal B vaccine Bexsero: a collaborative study. Vaccine. 2019;37(29):3761–69. doi:10.1016/j.vaccine.2018.05.073.
   PubMed Web of Science ®Google Scholar
• Hasiwa N, Daneshian M, Bruegger P, Fennrich S, Hochadel A, Hoffmann S, Rivera-Mariani FE, Rocker C, Schindler S, Spreitzer I, et al. Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test. Altex. 2013;30(2):169–208. doi:10.14573/altex.2013.2.169.
   PubMedGoogle Scholar
• Steeghs L, Keestra AM, van Mourik A, Uronen-Hansson H, van der Ley P, Callard R, Klein N, van Putten JPM. Differential activation of human and mouse Toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis. Infect Immun. 2008;76(8):3801–07. doi:10.1128/IAI.00005-08.
   PubMed Web of Science ®Google Scholar
• Stoddard MB, Pinto V, Keiser PB, Zollinger W. Evaluation of a whole-blood cytokine release assay for use in measuring endotoxin activity of group B Neisseria meningitidis vaccines made from lipid A acylation mutants. Clin Vaccine Immunol. 2010;17(1):98–107. doi:10.1128/CVI.00342-09.
   PubMedGoogle Scholar
• Schilling B, Hunt J, Gibson BW, Apicella MA. Site-specific acylation changes in the lipid A of Escherichia coli lpxL mutants grown at high temperatures. Innate Immun. 2014;20(3):269–82. doi:10.1177/1753425913490534.
   PubMed Web of Science ®Google Scholar
• Nichols WA, Raetz CRH, Clementz T, Smith AL, Hanson JA, Ketterer MR, Sunshine M, Apicella MA. htrB of Haemophilus influenzae: determination of biochemical activity and effects on virulence and lipooligosaccharide toxicity. Innate Immunity. 1997;4:163–72.
   Google Scholar
• Hone DM, Powell J, Crowley RW, Maneval D, Lewis GK. Lipopolysaccharide from an Escherichia coli htrB msbB mutant induces high levels of MIP-1 alpha and MIP-1 beta secretion without inducing TNF-alpha and IL-1 beta. J Hum Virol. 1998;1:251–56.
   PubMedGoogle Scholar
• Somerville JE Jr., Cassiano L, Bainbridge B, Cunningham MD, Darveau RP. A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide. J Clin Invest. 1996;97(2):359–65. doi:10.1172/JCI118423.
   PubMed Web of Science ®Google Scholar
• Leitner DR, Feichter S, Schild-Prufert K, Rechberger GN, Reidl J, Schild S. Lipopolysaccharide modifications of a cholera vaccine candidate based on outer membrane vesicles reduce endotoxicity and reveal the major protective antigen. Infect Immun. 2013;81(7):2379–93. doi:10.1128/IAI.01382-12.
   PubMed Web of Science ®Google Scholar
• Dowling DJ, Sanders H, Cheng WK, Joshi S, Brightman S, Bergelson I, Pietrasanta C, van Haren SD, van Amsterdam S, Fernandez J, et al. A meningococcal outer membrane vesicle vaccine incorporating genetically attenuated endotoxin dissociates inflammation from immunogenicity. Front Immunol. 2016;7:562. doi:10.3389/fimmu.2016.00562.
   PubMed Web of Science ®Google Scholar
• Bielig H, Rompikuntal PK, Dongre M, Zurek B, Lindmark B, Ramstedt M, Wai SN, Kufer TA. NOD-like receptor activation by outer membrane vesicles from vibrio cholerae non-O1 non-O139 strains is modulated by the quorum-sensing regulator HapR. Infect Immun. 2011;79(4):1418–27. doi:10.1128/IAI.00754-10.
   PubMed Web of Science ®Google Scholar
• Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, Le Bourhis L, Karrar A, Viala J, Mak J, et al. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol. 2010;12(3):372–85. doi:10.1111/j.1462-5822.2009.01404.x.
   PubMed Web of Science ®Google Scholar
• Launay O, Ndiaye AGW, Conti V, Loulergue P, Scire AS, Landre AM, Ferruzzi P, Nedjaai N, Schütte LD, Auerbach J, et al. Booster vaccination with GVGH Shigella sonnei 1790GAHB GMMA vaccine compared to single vaccination in unvaccinated healthy European adults: results from a Phase 1 clinical trial. Front Immunol. 2019;10:335. doi:10.3389/fimmu.2019.00335.
   PubMed Web of Science ®Google Scholar
• Gorringe AR, Taylor S, Brookes C, Matheson M, Finney M, Kerr M, Hudson M, Findlow J, Borrow R, Andrews N, et al. Phase I safety and immunogenicity study of a candidate meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles. Clin Vaccine Immunol. 2009;16(8):1113–20. doi:10.1128/CVI.00118-09.
   PubMedGoogle Scholar
• Spreitzer I. Evolution and Characteristics of the monocyte activation test (MAT). In: Williams KL, editor. Endotoxin detection and control in pharma, limulus, and mammalian systems. Cham: Springer International Publishing; 2019. p. 523–35. https://doi.org/10.1007/978-3-030-17148-3_14
   Google Scholar
• da Silva CC, Presgrave OA, Hartung T, de Moraes AM, Delgado IF. Applicability of the monocyte activation test (MAT) for hyperimmune sera in the routine of the quality control laboratory: comparison with the Rabbit pyrogen test (RPT). Toxicol In Vitro. 2016;32:70–75. doi:10.1016/j.tiv.2015.12.004.
   PubMed Web of Science ®Google Scholar
• Esposito S, Prymula R, Zuccotti GV, Xie F, Barone M, Dull PM, Toneatto D. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II). Hum Vaccin Immunother. 2014;10(7):2005–14. doi:10.4161/hv.29218.
   PubMed Web of Science ®Google Scholar
• Prymula R, Esposito S, Zuccotti GV, Xie F, Toneatto D, Kohl I, Dull PM. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I). Hum Vaccin Immunother. 2014;10(7):1993–2004. doi:10.4161/hv.28666.
   PubMed Web of Science ®Google Scholar