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Enhancing and Tailoring the Immunogenicity of Vaccines with Novel Adjuvants

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Abstract

Modern vaccine development is focused on purified subunit or recombinant antigens, which often have excellent safety profiles but reduced immunogenicity. Adjuvants are necessary vaccine components to enhance and shape immune responses to vaccines. Some adjuvants, such as aluminum salts and emulsions, have a long history and are approved for human use in many countries. Other adjuvants represent novel molecules or formulations being evaluated in advanced clinical trials or early phase research and development. In this chapter, we present a survey of current adjuvant development, including immunomodulatory molecules as well as particulate formulations, with a focus on four classes of adjuvants: alum, emulsions, TLR4 agonists, and TLR9 agonists. Throughout, we emphasize the importance of appropriate formulation and thorough physicochemical characterization. Rationally designed adjuvants will facilitate development of effective and safe next-generation vaccines.

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References

  • Aagaard C, Hoang TT, Izzo A, Billeskov R, Troudt J, Arnett K, Keyser A, Elvang T, Andersen P, Dietrich J (2009) Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose. PLoS One 4(6):e5930

    Article  PubMed  CAS  Google Scholar 

  • Agger EM, Rosenkrands I, Olsen AW, Hatch G, Williams A, Kritsch C, Lingnau K, von Gabain A, Andersen CS, Korsholm KS, Andersen P (2006) Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine 24(26):5452–5460

    Article  PubMed  CAS  Google Scholar 

  • Aichinger MC, Ortbauer M, Reipert S, Zauner W, Bogner P, Froschauer E, Nowikovsky K, Lingnau K, von Gabain A, Schweyen R, Henics T (2008) Unique membrane-interacting properties of the immunostimulatory cationic peptide KLKL(5)KLK (KLK). Cell Biol Int 32(11):1449–1458

    Article  PubMed  CAS  Google Scholar 

  • Aichinger MC, Ginzler M, Weghuber J, Zimmermann L, Riedl K, Schutz G, Nagy E, von Gabain A, Schweyen R, Henics T (2011) Adjuvating the adjuvant: facilitated delivery of an immunomodulatory oligonucleotide to TLR9 by a cationic antimicrobial peptide in dendritic cells. Vaccine 29(3):426–436

    Article  PubMed  CAS  Google Scholar 

  • Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732–738

    Article  PubMed  CAS  Google Scholar 

  • Allison AC (1999) Squalene and squalane emulsions as adjuvants. Methods 19(1):87–93

    Article  PubMed  CAS  Google Scholar 

  • Alvarez-Bravo J, Kurata S, Natori S (1994) Novel synthetic antimicrobial peptides effective against methicillin-resistant Staphylococcus aureus. Biochem J 302(Pt 2):535–538

    PubMed  CAS  Google Scholar 

  • Alving CR, Matyas GR (2005) Design and selection of vaccine adjuvants: principles and practice. In: Kaufmann SHE, Lambert PH (eds) The grand challenge for the future: vaccines for poverty-related diseases from bench to field. Verlag, Basel, pp 99–118

    Google Scholar 

  • Anderson RC, Fox CB, Dutill TS, Shaverdian N, Evers TL, Poshusta GR, Chesko J, Coler RN, Friede M, Reed SG, Vedvick TS (2010) Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations. Colloids Surf B Biointerfaces 75:123–132

    Article  PubMed  CAS  Google Scholar 

  • Antimisiaris SG, Kallinteri P, Fatouros DG (2008) Liposomes and drug delivery. In: Gad SC (ed) Pharmaceutical manufacturing handbook: production and processes. Wiley, Hoboken, NJ, pp 443–534

    Chapter  Google Scholar 

  • Baldridge JR, Crane RT (1999) Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines. Methods 19(1):103–107

    Article  PubMed  CAS  Google Scholar 

  • Baldwin SL, Bertholet S, Kahn M, Zharkikh I, Ireton GC, Vedvick TS, Reed SG, Coler RN (2009a) Intradermal immunization improves protective efficacy of a novel TB vaccine candidate. Vaccine 27:3063–3071

    Article  PubMed  CAS  Google Scholar 

  • Baldwin SL, Shaverdian N, Goto Y, Duthie MS, Raman VS, Evers T, Mompoint F, Vedvick TS, Bertholet S, Coler RN, Reed SG (2009b) Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion. Vaccine 27:5956–5963

    Article  PubMed  CAS  Google Scholar 

  • Barchet W, Wimmenauer V, Schlee M, Hartmann G (2008) Accessing the therapeutic potential of immunostimulatory nucleic acids. Curr Opin Immunol 20(4):389–395

    Article  PubMed  CAS  Google Scholar 

  • Baudner BC, Ronconi V, Casini D, Tortoli M, Kazzaz J, Singh M, Hawkins LD, Wack A, O’Hagan DT (2009) MF59 emulsion is an effective delivery system for a synthetic TLR4 agonist (E6020). Pharm Res 26(6):1477–1485

    Article  PubMed  CAS  Google Scholar 

  • Bertholet S, Goto Y, Carter L, Bhatia A, Howard RF, Carter D, Coler RN, Vedvick TS, Reed SG (2009) Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine 27:7036–7045

    Article  PubMed  CAS  Google Scholar 

  • Bertholet S, Ireton GC, Ordway DJ, Windish HP, Pine SO, Kahn M, Phan T, Orme IM, Vedvick TS, Baldwin SL, Coler RN, Reed SG (2010) A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med 2:53ra74

    Article  PubMed  CAS  Google Scholar 

  • Brazolot Millan CL, Weeratna R, Krieg AM, Siegrist CA, Davis HL (1998) CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc Natl Acad Sci USA 95(26):15553–15558

    Article  PubMed  CAS  Google Scholar 

  • Buschle M, Schmidt W, Zauner W, Mechtler K, Trska B, Kirlappos H, Birnstiel ML (1997) Transloading of tumor antigen-derived peptides into antigen-presenting cells. Proc Natl Acad Sci USA 94(7):3256–3261

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Li P, Yin Y, Cai X, Huang Z, Chen J, Dong L, Zhang J (2010) The promotion of type 1 T helper cell responses to cationic polymers in vivo via toll-like receptor-4 mediated IL-12 secretion. Biomaterials 31:8172–8180

    Article  PubMed  CAS  Google Scholar 

  • Chollet JL, Jozwiakowski MJ, Phares KR, Reiter MJ, Roddy PJ, Schultz HJ, Ta QV, Tomai MA (1999) Development of a topically active imiquimod formulation. Pharm Dev Technol 4(1):35–43

    PubMed  CAS  Google Scholar 

  • Clapp T, Siebert P, Chen D, Jones Braun L (2010) Vaccines with aluminum-containing adjuvants: optimizing vaccine efficacy and thermal stability. J Pharm Sci 100(2):388–401

    Article  PubMed  CAS  Google Scholar 

  • Cleland JL, Kensil CR, Lim A, Jacobsen NE, Basa L, Spellman M, Wheeler DA, Wu JY, Powell MF (1996) Isomerization and formulation stability of the vaccine adjuvant QS-21. J Pharm Sci 85(1):22–28

    Article  PubMed  CAS  Google Scholar 

  • Clements DE, Coller BA, Lieberman MM, Ogata S, Wang G, Harada KE, Putnak JR, Ivy JM, McDonell M, Bignami GS, Peters ID, Leung J, Weeks-Levy C, Nakano ET, Humphreys T (2010) Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. Vaccine 28(15):2705–2715

    Article  PubMed  CAS  Google Scholar 

  • Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ, Raman VS, Lu X, DeVos J, Hancock K, Katz JM, Vedvick TS, Duthie MS, Clegg CH, Van Hoeven N, Reed SG (2010) A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One 5:e13677

    Article  PubMed  CAS  Google Scholar 

  • Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, Laughlin EM, Duthie MS, Fox CB, Carter D, Friede M, Vedvick TS, Reed SG (2011) Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One 6(1):e16333

    Article  PubMed  CAS  Google Scholar 

  • De Gregorio E, Tritto E, Rappuoli R (2008) Alum adjuvanticity: unraveling a century old mystery. Eur J Immunol 38:2068–2071

    Article  PubMed  CAS  Google Scholar 

  • Dupuis M, Murphy TJ, Higgins D, Ugozzoli M, van Nest G, Ott G, McDonald DM (1998) Dendritic cells internalize vaccine adjuvant after intramuscular injection. Cell Immunol 186(1):18–27

    Article  PubMed  CAS  Google Scholar 

  • Dupuis M, McDonald DM, Ott G (1999) Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection in mice. Vaccine 18(5–6):434–439

    Article  PubMed  CAS  Google Scholar 

  • Duthie MS, Windish HP, Fox CB, Reed SG (2011) Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 239:1–19

    Article  Google Scholar 

  • Edelman R (1980) Vaccine adjuvants. Rev Infect Dis 2:370–383

    Article  PubMed  CAS  Google Scholar 

  • Exley C, Siesjo P, Eriksson H (2010) The immunobiology of aluminium adjuvants: how do they really work? Trends Immunol 31(3):103–109

    Article  PubMed  CAS  Google Scholar 

  • Fox CB (2009) Squalene emulsions for parenteral vaccine and drug delivery. Molecules 14(9):3286–3312

    Article  PubMed  CAS  Google Scholar 

  • Fox CB, Harris JM (2010) Confocal Raman microscopy for simultaneous monitoring of partitioning and disordering of tricyclic antidepressants in phospholipid vesicle membranes. J Raman Spectrosc 41:498–507

    Article  CAS  Google Scholar 

  • Fox CB, Uibel RH, Harris JM (2007) Detecting phase transitions in phosphatidylcholine vesicles by Raman microscopy and self-modeling curve resolution. J Phys Chem B 111(39):11428–11436

    Article  PubMed  CAS  Google Scholar 

  • Fox CB, Anderson RC, Dutill TS, Goto Y, Reed SG, Vedvick TS (2008) Monitoring the effects of component structure and source on formulation stability and adjuvant activity of oil-in-water emulsions. Colloids Surf B Biointerfaces 65(1):98–105

    Article  PubMed  CAS  Google Scholar 

  • Fox CB, Dutill TS, Chesko J, Anderson RC, Reed SG, Vedvick TS (2010a) Characterization of aluminum hydroxide gel and oil-in-water emulsion formulations containing CpG ODNs. Biopharm Int 23(10):S14–S19

    Google Scholar 

  • Fox CB, Friede M, Reed SG, Ireton GC (2010b) Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants. In: Wang X, Quinn PJ (eds) Endotoxins: structure, function and recognition, vol 53, Subcellular biochemistry. Springer, New York, pp 303–321

    Chapter  Google Scholar 

  • Fox CB, Lin S, Sivananthan SJ, Dutill TS, Forseth KT, Reed SG, Vedvick TS (2011) Effects of emulsifier concentration, composition, and order of addition in squalene-phosphatidylcholine oil-in-water emulsions. Pharm Dev Technol 16(5):511–519. doi:10.3109/10837450.2010.495397

    Article  PubMed  CAS  Google Scholar 

  • Freund J, Bonanto MV (1944) The effect of paraffin oil, lanolin-like substances and killed tubercle bacilli on immunization with diphtheric toxoid and bact. Typhosum J Immunol 48:325–334

    Google Scholar 

  • Freund J, Casals J, Hosmer EP (1937) Sensitization and antibody formation after injection of tubercle bacilli and paraffin oil. Proc Soc Exp Biol Med 37(37):509–513

    CAS  Google Scholar 

  • Fritz JH, Brunner S, Birnstiel ML, Buschle M, Gabain A, Mattner F, Zauner W (2004) The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens. Vaccine 22(25–26):3274–3284

    Article  PubMed  CAS  Google Scholar 

  • Garcon N (2010) Preclinical development of AS04. Methods Mol Biol 626:15–27

    Article  PubMed  CAS  Google Scholar 

  • Garidel P, Rappolt M, Schromm AB, Howe J, Lohner K, Andra J, Koch MH, Brandenburg K (2005) Divalent cations affect chain mobility and aggregate structure of lipopolysaccharide from Salmonella minnesota reflected in a decrease of its biological activity. Biochim Biophys Acta 1715(2):122–131

    Article  PubMed  CAS  Google Scholar 

  • Granger C, Barey P, Toutain J, Cansell M (2005) Direct quantification of protein partitioning in oil-in-water emulsion by front-face fluorescence: avoiding the need for centrifugation. Colloids Surf B Biointerfaces 43(3–4):158–162

    Article  PubMed  CAS  Google Scholar 

  • Hajjar AM, Ernst RK, Tsai JH, Wilson CB, Miller SI (2002) Human Toll-like receptor 4 recognizes host-specific LPS modifications. Nat Immunol 3(4):354–359

    Article  PubMed  CAS  Google Scholar 

  • Hansen B, Sokolovska A, HogenEsch H, Hem SL (2007) Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response. Vaccine 25(36):6618–6624

    Article  PubMed  CAS  Google Scholar 

  • Hem SL, HogenEsch H (2007) Aluminum-containing adjuvants: properties, formulation, and use. In: Singh M (ed) Vaccine adjuvants and delivery systems. Wiley, Hoboken, NJ, pp 81–114

    Chapter  Google Scholar 

  • Hilleman MR (1966) Critical appraisal of emulsified oil adjuvants applied to viral vaccines. Prog Med Virol 8:131–182

    PubMed  CAS  Google Scholar 

  • Hilleman MR (1999) Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology. Immunol Rev 170:7–27

    Article  PubMed  CAS  Google Scholar 

  • Hirabayashi K, Yano J, Inoue T, Yamaguchi T, Tanigawara K, Smyth GE, Ishiyama K, Ohgi T, Kimura K, Irimura T (1999) Inhibition of cancer cell growth by polyinosinic-polycytidylic acid/cationic liposome complex: a new biological activity. Cancer Res 59(17):4325–4333

    PubMed  CAS  Google Scholar 

  • Hui GS, Hashimoto CN (2008) Adjuvant formulations possess differing efficacy in the potentiation of antibody and cell mediated responses to a human malaria vaccine under selective immune genes knockout environment. Int Immunopharmacol 8(7):1012–1022

    Article  PubMed  CAS  Google Scholar 

  • Ioannou XP, Gomis SM, Hecker R, Babiuk LA, van Drunen Littel-van den Hurk S (2003) Safety and efficacy of CpG-containing oligodeoxynucleotides as immunological adjuvants in rabbits. Vaccine 21(27–30):4368–4372

    Article  PubMed  CAS  Google Scholar 

  • Jurgens G, Muller M, Koch MH, Brandenburg K (2001) Interaction of hemoglobin with enterobacterial lipopolysaccharide and lipid A. Physicochemical characterization and biological activity. Eur J Biochem 268(15):4233–4242

    Article  PubMed  CAS  Google Scholar 

  • Kamath AT, Valenti MP, Rochat AF, Agger EM, Lingnau K, von Gabain A, Andersen P, Lambert PH, Siegrist CA (2008a) Protective anti-mycobacterial T Cell responses through exquisite in vivo activation of vaccine-targeted dendritic cells. Eur J Immunol 38:1247–1256

    Article  PubMed  CAS  Google Scholar 

  • Kamath AT, Rochat AF, Valenti MP, Agger EM, Lingnau K, Andersen P, Lambert PH, Siegrist CA (2008b) Adult-like anti-mycobacterial T cell and in vivo dendritic cell responses following neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant. PLoS One 3:e3683

    Article  PubMed  CAS  Google Scholar 

  • Kawahara K, Tsukano H, Watanabe H, Lindner B, Matsuura M (2002) Modification of the structure and activity of lipid A in Yersinia pestis lipopolysaccharide by growth temperature. Infect Immun 70(8):4092–4098

    Article  PubMed  CAS  Google Scholar 

  • Kedmi R, Ben-Arie N, Peer D (2010) The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation. Biomaterials 31(26):6867–6875

    Article  PubMed  CAS  Google Scholar 

  • Kensil CR (2000) QS-21 adjuvant. In: O’Hagan DT (ed) Vaccine adjuvants: preparation methods and research protocols. Humana, Totowa, NJ, pp 259–271

    Chapter  Google Scholar 

  • Kim JI, Iwai H, Kurata S, Takahashi M, Masuda K, Shimada I, Natori S, Arata Y, Sato K (1994) Synthesis and characterization of sapecin and sapecin B. FEBS Lett 342(2):189–192

    Article  PubMed  CAS  Google Scholar 

  • Klade CS, Wedemeyer H, Berg T, Hinrichsen H, Cholewinska G, Zeuzem S, Blum H, Buschle M, Jelovcan S, Buerger V, Tauber E, Frisch J, Manns MP (2008) Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41. Gastroenterology 134(5):1385–1395

    Article  PubMed  CAS  Google Scholar 

  • Klinman DM, Klaschik S, Sato T, Tross D (2009) CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases. Adv Drug Deliv Rev 61(3):248–255

    Article  PubMed  CAS  Google Scholar 

  • Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, Bergen IM, Castillo R, Lambrecht BN, Tschopp J (2008) Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 181(6):3755–3759

    PubMed  CAS  Google Scholar 

  • Linghua Z, Xingshan T, Fengzhen Z (2006) The efficacy of CpG oligodinucleotides, in combination with conventional adjuvants, as immunological adjuvants to swine streptococcic septicemia vaccine in piglets in vivo. Int Immunopharmacol 6(8):1267–1276

    Article  PubMed  CAS  Google Scholar 

  • Lousada-Dietrich S, Jogdand PS, Jepsen S, Pinto VV, Ditlev SB, Christiansen M, Larsen SO, Fox CB, Raman VS, Howard RF, Vedvick TS, Ireton G, Carter D, Reed SG, Theisen M (2011) A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2 – A GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine 29(17):3284–3292

    Article  PubMed  CAS  Google Scholar 

  • Maraskovsky E, Schnurr M, Wilson NS, Robson NC, Boyle J, Drane D (2009) Development of prophylactic and therapeutic vaccines using the ISCOMATRIX adjuvant. Immunol Cell Biol 87:371–376

    Article  PubMed  CAS  Google Scholar 

  • Mattner F, Fleitmann JK, Lingnau K, Schmidt W, Egyed A, Fritz J, Zauner W, Wittmann B, Gorny I, Berger M, Kirlappos H, Otava A, Birnstiel ML, Buschle M (2002) Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens. Cancer Res 62(5):1477–1480

    PubMed  CAS  Google Scholar 

  • McKee AS, Munks MW, Marrack P (2007) How do adjuvants work? Important considerations for new generation adjuvants. Immunity 27(5):687–690

    Article  PubMed  CAS  Google Scholar 

  • McKenzie A, Watt M, Gittleson C (2010) ISCOMATRIX™ vaccines: safety in human clinical studies. Hum Vaccin 6:237–246

    Article  CAS  Google Scholar 

  • Middleton D, Rockman S, Pearse M, Barr I, Lowther S, Klippel J, Ryan D, Brown L (2009) Evaluation of vaccines for H5N1 influenza virus in ferrets reveals the potential for protective single-shot immunization. J Virol 83(15):7770–7778

    Article  PubMed  CAS  Google Scholar 

  • Morein B, Hu K, Lovgren K, D’Hondt E (2007) New ISCOMs meet unsettled vaccine demands. In: Singh M (ed) Vaccine adjuvants and delivery systems. Wiley, Hoboken, NJ, pp 191–222

    Chapter  Google Scholar 

  • Mosca F, Tritto E, Muzzi A, Monaci E, Bagnoli F, Iavarone C, O’Hagan D, Rappuoli R, De Gregorio E (2008) Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA 105(30):10501–10506

    Article  PubMed  CAS  Google Scholar 

  • Mueller M, Lindner B, Kusumoto S, Fukase K, Schromm AB, Seydel U (2004) Aggregates are the biologically active units of endotoxin. J Biol Chem 279(25):26307–26313

    Article  PubMed  CAS  Google Scholar 

  • Norden TP, Siekmann B, Lundquist S, Malmsten M (2001) Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration. Eur J Pharm Sci 13(4):393–401

    Article  PubMed  CAS  Google Scholar 

  • O’Hagan DT, Singh M, Kazzaz J, Ugozzoli M, Briones M, Donnelly J, Ott G (2002) Synergistic adjuvant activity of immunostimulatory DNA and oil/water emulsions for immunization with HIV p55 gag antigen. Vaccine 20:3389–3398

    Article  PubMed  Google Scholar 

  • Olafsdottir TA, Lingnau K, Nagy E, Jonsdottir I (2009) IC31, a two-component novel adjuvant mixed with a conjugate vaccine enhances protective immunity against pneumococcal disease in neonatal mice. Scand J Immunol 69:194–202

    Article  PubMed  CAS  Google Scholar 

  • Ott G, Van Nest G (2007) Development of vaccine adjuvants: a historical perspective. In: Singh M (ed) Vaccine adjuvants and delivery systems. Wiley, Hoboken, NJ, pp 1–31

    Chapter  Google Scholar 

  • Ott G, Singh M, Kazzaz J, Briones M, Soenawan E, Ugozzoli M, O’Hagan DT (2002) A cationic sub-micron emulsion (MF59/DOTAP) is an effective delivery system for DNA vaccines. J Control Release 79:1–5

    Article  PubMed  CAS  Google Scholar 

  • Owusu-Agyei S, Ansong D, Asante K, Kwarteng Owusu S, Owusu R, Wireko Brobby NA, Dosoo D, Osei Akoto A, Osei-Kwakye K, Adjei EA, Boahen KO, Sylverken J, Adjei G, Sambian D, Apanga S, Kayan K, Vekemans J, Ofori-Anyinam O, Leach A, Lievens M, Demoitie MA, Dubois MC, Cohen J, Ballou WR, Savarese B, Chandramohan D, Gyapong JO, Milligan P, Antwi S, Agbenyega T, Greenwood B, Evans J (2009) Randomized controlled trial of RTS, S/AS02D and RTS, S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. PLoS One 4(10):e7302

    Article  PubMed  CAS  Google Scholar 

  • Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458(7242):1191–1195

    Article  PubMed  CAS  Google Scholar 

  • Pichyangkul S, Gettayacamin M, Miller RS, Lyon JA, Angov E, Tongtawe P, Ruble DL, Heppner DG Jr, Kester KE, Ballou WR, Diggs CL, Voss G, Cohen JD, Walsh DS (2004) Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum. Vaccine 22(29–30):3831–3840

    Article  PubMed  CAS  Google Scholar 

  • Poltl-Frank F, Zurbriggen R, Helg A, Stuart F, Robinson J, Gluck R, Pluschke G (1999) Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide-based vaccine. Clin Exp Immunol 117(3):496–503

    Article  PubMed  CAS  Google Scholar 

  • Potter CW, Jennings R (2003) Effect of priming on subsequent response to inactivated influenza vaccine. Vaccine 21(9–10):940–945

    Article  PubMed  CAS  Google Scholar 

  • Prchal M, Pilz A, Simma O, Lingnau K, von Gabain A, Strobl B, Muller M, Decker T (2009) Type I interferons as mediators of immune adjuvants for T- and B cell-dependent acquired immunity. Vaccine 27(Suppl 6):G17–G20

    Article  PubMed  CAS  Google Scholar 

  • Ragupathi G, Damani P, Deng K, Adams MM, Hang J, George C, Livingston PO, Gin DY (2010) Preclinical evaluation of the synthetic adjuvant SQS-21 and its constituent isomeric saponins. Vaccine 28(26):4260–4267

    Article  PubMed  CAS  Google Scholar 

  • Raman VS, O’Donnell J, Bailor HR, Goto W, Lahiri R, Gillis TP, Reed SG, Duthie MS (2009) Vaccination with the ML0276 antigen reduces local inflammation but not bacterial burden during experimental Mycobacterium leprae infection. Infect Immun 77:5623–5630

    Article  PubMed  CAS  Google Scholar 

  • Reddy LH, Couvreur P (2009) Squalene: a natural triterpene for use in disease management and therapy. Adv Drug Deliv Rev 61(15):1412–1426

    Article  PubMed  CAS  Google Scholar 

  • Reed SG, Bertholet S, Coler RN, Friede M (2009) New horizons in adjuvants for vaccine development. Trends Immunol 30:23–32

    Article  PubMed  CAS  Google Scholar 

  • Richards RL, Swartz GM Jr, Schultz C, Hayre MD, Ward GS, Ballou WR, Chulay JD, Hockmeyer WT, Berman SL, Alving CR (1989) Immunogenicity of liposomal malaria sporozoite antigen in monkeys: adjuvant effects of aluminium hydroxide and non-pyrogenic liposomal lipid A. Vaccine 7(6):506–512

    Article  PubMed  CAS  Google Scholar 

  • Riedl K, Riedl R, von Gabain A, Nagy E, Lingnau K (2008) The novel adjuvant IC31 strongly improves influenza vaccine-specific cellular and humoral immune responses in young adult and aged mice. Vaccine 26(27–28):3461–3468

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SA, Yang JC, Kammula US, Hughes MS, Restifo NP, Schwarz SL, Morton KE, Laurencot CM, Sherry RM (2010) Different adjuvanticity of incomplete freund’s adjuvant derived from beef or vegetable components in melanoma patients immunized with a peptide vaccine. J Immunother 33(6):626–629

    Article  PubMed  CAS  Google Scholar 

  • Salem AK, Weiner GJ (2009) CpG oligonucleotides as immunotherapeutic adjuvants: innovative applications and delivery strategies. Adv Drug Deliv Rev 61(3):193–194

    Article  PubMed  CAS  Google Scholar 

  • Schellack C, Prinz K, Egyed A, Fritz JH, Wittmann B, Ginzler M, Swatosch G, Zauner W, Kast C, Akira S, von Gabain A, Buschle M, Lingnau K (2006) IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine 24(26):5461–5472

    Article  PubMed  CAS  Google Scholar 

  • Schnurr M, Orban M, Robson NC, Shin A, Braley H, Airey D, Cebon J, Maraskovsky E, Endres S (2009) ISCOMATRIX adjuvant induces efficient cross-presentation of tumor antigen by dendritic cells via rapid cytosolic antigen delivery and processing via tripeptidyl peptidase II. J Immunol 182:1253–1259

    Article  PubMed  CAS  Google Scholar 

  • Schultze V, D’Agosto V, Wack A, Novicki D, Zorn J, Hennig R (2008) Safety of MF59 adjuvant. Vaccine 26(26):3209–3222

    Article  PubMed  CAS  Google Scholar 

  • Seubert A, Monaci E, Pizza M, O’Hagan DT, Wack A (2008) The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol 180(8):5402–5412

    PubMed  CAS  Google Scholar 

  • Seydel U, Oikawa M, Fukase K, Kusumoto S, Brandenburg K (2000) Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity. Eur J Biochem 267(10):3032–3039

    Article  PubMed  CAS  Google Scholar 

  • Singh M, Ott G, Kazzaz J, Ugozzoli M, Briones M, Donnelly J, O’Hagan DT (2001) Cationic microparticles are an effective delivery system for immune stimulatory CpG DNA. Pharm Res 18:1476–1479

    Article  PubMed  CAS  Google Scholar 

  • Singh M, Chesko J, Kazzaz J, Ugozolli M, Malyala P, O’Hagan DT (2007) Surface-charged poly(lactide-co-glycolide) microparticles as novel antigen delivery systems. In: Singh M (ed) Vaccine adjuvants and delivery systems. Wiley, Hoboken, NJ, pp 223–248

    Chapter  Google Scholar 

  • Soliakov A, Harris JR, Watkinson A, Lakey JH (2010) The structure of Yersinia pestis Caf1 polymer in free and adjuvant bound states. Vaccine 28(35):5746–5754

    Article  PubMed  CAS  Google Scholar 

  • Steeghs L, Keestra AM, van Mourik A, Uronen-Hansson H, van der Ley P, Callard R, Klein N, van Putten JP (2008) Differential activation of human and mouse Toll-like receptor 4 by the adjuvant candidate LpxL1 of Neisseria meningitidis. Infect Immun 76(8):3801–3807

    Article  PubMed  CAS  Google Scholar 

  • Stewart-Tull DE (2010) Freund’s complete and incomplete adjuvants, preparation, and quality control standards for experimental laboratory animals use. Methods Mol Biol 626:59–72

    Article  PubMed  CAS  Google Scholar 

  • van Dissel JT, Arend SM, Prins C, Bang P, Tingskov PN, Lingnau K, Nouta J, Klein MR, Rosenkrands I, Ottenhoff TH, Kromann I, Doherty TM, Andersen P (2010) Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naive human volunteers. Vaccine 28(20):3571–3581

    Article  PubMed  CAS  Google Scholar 

  • Vogel FR, Caillet C, Kusters IC, Haensler J (2009) Emulsion-based adjuvants for influenza vaccines. Expert Rev Vaccines 8(4):483–492

    Article  PubMed  CAS  Google Scholar 

  • Wack A, Baudner BC, Hilbert AK, Manini I, Nuti S, Tavarini S, Scheffczik H, Ugozzoli M, Singh M, Kazzaz J, Montomoli E, Del Guidice G, Rappuoli R, O’Hagan DT (2008) Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice. Vaccine 26:552–561

    Article  PubMed  CAS  Google Scholar 

  • Zaks K, Jordan M, Guth A, Sellins K, Kedl R, Izzo A, Bosio C, Dow S (2006) Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J Immunol 176(12):7335–7345

    PubMed  CAS  Google Scholar 

  • Zhengrong C, Qiu F (2006) Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model. Cancer Immunol Immunother 55:1267–1279

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Infectious Disease Research Institute, 1124 Columbia Street, Ste 400, Seattle, WA, 98104, USA

    Christopher B. Fox

  2. Intercell AG, Wien, Austria

    Benjamin Wizel

  3. Infectious Disease Research Institute, Seattle, WA, USA

    Steven G. Reed

  4. Immune Design Corporation, Seattle, WA, USA

    Steven G. Reed

  5. Novartis Vaccines, Cambridge, MA, USA

    Derek T. O’Hagan

Authors
  1. Christopher B. Fox
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  2. Benjamin Wizel
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  3. Steven G. Reed
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  4. Derek T. O’Hagan
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Corresponding author

Correspondence to Christopher B. Fox .

Editor information

Editors and Affiliations

  1. Intercell AG, Campus Vienna Biocenter 3, Vienna, 1030, Austria

    Alexander von Gabain

  2. Intercell AG, Campus Vienna Biocenter 3, Vienna, 1030, Austria

    Christoph Klade

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Fox, C.B., Wizel, B., Reed, S.G., O’Hagan, D.T. (2012). Enhancing and Tailoring the Immunogenicity of Vaccines with Novel Adjuvants. In: von Gabain, A., Klade, C. (eds) Development of Novel Vaccines. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0709-6_3

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