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Review

Carbohydrate-based vaccine adjuvants – discovery and development

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Bibliography

  • Minichiello V. New vaccine technology, what do you need to know? J Am Acad Nurse Pract 2002;14(2):73-81
  • Lima KM, dos Santos SA, Rodrigues JMJr, et al. Vaccine adjuvant: it makes the difference. Vaccine 2004;22(19):2374-9
  • Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol 2004;82(5):488-96
  • Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med 2013;19(12):1597-608
  • Vogel FR. Adjuvants in perspective. In: Brown F, Haaheim LR, editors. Modulation of the immune response to vaccine antigens. Dev Biol Stand 1998;92:241-8
  • Glenny AT, Pope CG, Waddington H, et al. The antigenic value of toxoid precipitated by potassium alum. J Pathol Bacteriol 1926;29:38-9
  • Gupta RK. Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 1998;32:155-72
  • Gherardi RK, Coquet M, Cherin P, et al. Macrophagic myofasciitis: an emerging entity. Groupe d’Etudes et recherchesur les maladies musculaires acquises et dysimmunitaires (GERMMAD) del’Association Francaise contre les Myopathies (AFM). Lancet 1998;352(9125):347-52
  • Vera-Lastra O, Medina G, Cruz-Dominguez MP, et al. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld’s syndrome): clinical and immunological spectrum. Expert Rev Clin Immunol 2013;4(4):361-73
  • Petrovsky N, Cooper PD. Carbohydrate-based immune adjuvants. Expert Rev Vaccine 2011;10(4):523-37
  • Audibert FM, Lise LD. Adjuvants: current status, clinical perspectives and future prospects. Immunol Today 1993;14(6):281-4
  • Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002;71:635-700
  • Rietschel ET, Kirikae T, Schade FU, et al. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J 1994;8(2):217-25
  • Kim HM, Park BS, Kim JI, et al. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 2007;130(5):906-17
  • Ohto U, Fukase K, Miyake K, et al. Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa. Science 2007;316(5831):1632-4
  • Park BS, Song DH, Kim HM, et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009;458(7242):1191-5
  • Cluff CW. Monophosphoryl lipid (MPL) as an adjuvant for anti-cancer vaccines: clinical results. Adv Exp Med Biol 2009;667:111-23
  • Masihi KN, Lange W, Brehmer W, et al. Immunobiological activities of nontoxic lipid A: enhancement of nonspecific resistance in combination with trehalose dimycolate against viral infection and adjuvant effects. Int J Immunopharmacol 1986;8(3):339-45
  • Tomai MA, Johnson AG. T cell and interferon-gamma involvement in the adjuvant action of a detoxified endotoxin. J Biol Resp Modifiers 1989;8(6):625-30
  • Baldrick P, Richardson D, Elliott G, et al. Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant. Regul Toxicol Pharmacol 2002;35(3):398-413
  • Johnson DA, Sowell GC, Johnson LC, et al. Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs). Bioorg Med Chem Lett 1999;9(15):2273-8
  • Evans JT, Cluff CW, Johnson DA, et al. Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi. 529. Expert Rev Vaccines 2003;2(2):89-99
  • Fox CB, Friede M, Reed SG, et al. Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants. Subcell Biochem 2010;53:303-21
  • Cekic C, Casella CR, Eaves CA, et al. Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A. J Biol Chem 2009;284(46):31982-91
  • Garçon N, Chomez P, Van Mechelen M. GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines 2007;6(5):723-39
  • Garcon N, Van Mechelen M. Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Expert Rev Vaccines 2011;10(4):471-86
  • Destexhe E, Grosdidier E, Baudson N, et al. Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys. J Appl Toxicol 2015;35(7):717-28
  • Destexhe E, Stannard D, Wilby OK, et al. Nonclinical reproductive and developmental safety evaluation of theMAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment. Reprod Toxicol 2015;51:90-105
  • Segal L, Morelle D, Blee M, et al. Local tolerance and systemic toxicity of single and repeated intramuscular administrations of two different formulations of the RTS,S malaria candidate vaccine in rabbits. Regul Toxicol Pharmacol 2015;71(2):269-78
  • RTS, S clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 2015. [Epub ahead of print]
  • Didierlaurent AM, Collignon C, Bourguignon P, et al. Enhancement of adaptive immunity by the human vaccine adjuvant AS01 depends on activated dendritic cells. J Immunol 2014;193(4):1920-30
  • Leroux-Roels G, Van Belle P, Vandepapeliere P, et al. Vaccine adjuvant systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination. Vaccine 2015;33(8):1084-91
  • Segal L, Morelle D, Kaaber K, et al. Non-clinical safety assessment of single and repeated intramuscular administration of a human papillomavirus-16/18 vaccine in rabbits and rats. J Appl Toxicol 2015. [Epub ahead of print]
  • Segal L, Wilby OK, Willoughby CR, et al. Evaluation of the intramuscular administration of Cervarix™ vaccine on fertility, pre- and post-natal development in rats. Reprod Toxicol 2011;31(1):111-20
  • Didierlaurent AM, Morel A, Lockman L, et al. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol 2009;183(10):6186-97
  • Paavonen J, Jenkins D, Bosch FX, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007;369(9580):2161-70
  • Harper DM, Franco EL, Wheeler CM, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364(9447):1757-65
  • Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006;367(9518):1247-55
  • Kundi M. New hepatitis B vaccine formulated with an improved adjuvant system. Expert Rev Vaccines 2007;6(2):133-40
  • Gawchik SM, Saccar CL. Pollinex quattro tree: allergy vaccine. Expert Opin Biol Ther 2009;9(3):377-82
  • Pimm MV, Baldwin RW, Polonsky J, et al. Immunotherapy of an ascitic rat hepatoma with cord fact or (trehalose-6, 6’-dimycolate) and synthetic analogs. Int J Cancer 1979;24:780-5
  • Lemaire G, Tenu JP, Petit JF, Lederer E. Natural and synthetic trehalose diesters as immunomodulators. Med Res Rev 1986;6:243-74
  • Sueoka E, Nishiwaki S, Okabe S, et al. Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-α release in mouse lung tissues. Jpn J Cancer Res 1995;86(8):749-55
  • Masihi KN, Brehmer W, Lange W, Ribi E. Effects of mycobacterial fractions and muramyl dipeptide on the resistance of mice to aerogenic influenza virus infection. Int J Immunopharmacol 1983;5(5):403-10
  • Pimm MV, Baldwin RW, Polonsky J, Lederer E. Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6,6 ’-dimycolate) and synthetic analogues. Int J Cancer 1979;24:780-5
  • Sakurai T, Saiki I, Ishida H, et al. Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice. Vaccine 1989;7(3):269-74
  • Werninghaus K, Babiak A, Gross O, et al. Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation. J Exp Med 2009;206:89-97
  • Schoenen H, Bodendorfer B, Hitchens K, et al. Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analogue trehalosedibehenate1. J Immunol 2010;184(6):2756-60
  • Schweneker K, Gorka O, Schweneker M, et al. The mycobacterial cord factor adjuvant analogue trehalose-6, 6’-dibehenate (TDB) activates the Nlrp3 inflammasome. Immunobiology 2013;218:664-73
  • Olds GR, Chedid L, Lederer E, Mahmoud AA. Induction of resistance to Schistosoma mansoni by natural cord factor and synthetic lower homologs. J Infect Dis 1980;141:473-8
  • Davidsen J, Rosenkrands I, Christensen D, et al. Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6′-dibehenate)- A novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta 2005;1718:22-31
  • Lindenstrom T, Knudsen NP, Agger EM, Andersen P. Control of chronic mycobacterium tuberculosis infection by CD4 KLRG1-IL-2-secreting central memory cells. J Immunol 2013;190(12):6311-19
  • Lindenstrom T, Woodworth J, Dietrich J, et al. Vaccine-induced th17 cells are maintained long-term postvaccination as a distinct and phenotypically stable memory subset. Infect Immun 2012;80(10):3533-44
  • Aagaard C, Hoang T, Dietrich J, et al. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 2011;17(2):189-94
  • Ottenhoff TH. New pathways of protective and pathological host defense to mycobacteria. Trends Microbiol 2012;20(9):419-28
  • Henson D, van Dissel JT, Joosten SA, et al. Vaccination with a Hybrid 1 (H1) fusion protein combined with a liposomal adjuvant (CAF01) induced antigen specific T-cells 3 years post vaccination in a human clinical trial. J Immunol 2014;192(Suppl 1):141-16
  • van Dissel JT, Joosten SA, Hoff AT, et al. A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human. Vaccine 2014;32(52):7098-107
  • Skene CD, Sutton P. Saponin-adjuvanted particulate vaccines for clinical use. Methods 2006;40(1):53-9
  • Kensil CR, Kammer R. QS-21: a water-soluble triterpene glycoside adjuvant. Exp Opin Invest Drugs 1998;7(9):1475-82
  • Dalsgaard K. Thin layer chromatographic finger printing of commercially available saponins. Dan Tidsskr Farm 1970;44:327-31
  • Kersten GFA, Teerlink T, Derks HJ. Incorporation of the major outer-membrane protein of Neisseria gonorrhoeae in saponin-lipid complexes (Iscoms) - chemical-analysis, some structural features, and comparison of their immunogenicity with 3 other antigen delivery systems. Infect Immun 1988;56:432-48
  • Kensil CR, Patel U, Lennick M, et al. Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J Immunol 1991;146(2):431-7
  • Dalsgaard K. Adjuvants. Vet Immunol Immunopathol 1987;17(1-4):145-52
  • Gin DY, Slovin SF. Enhancing immunogenicity of cancer vaccines: QS-21 as an immune adjuvant. Curr Drug Ther 2011;6(3):207-12
  • Kensil CR, Wu JY, Soltysik S. Structural and immunological characterization of the vaccine adjuvant QS-21. Pharm Biotechnol 1995;6:525-41
  • Kensil CR, Soltysik S, Wheeler DA, et al. Structure/function studies on QS-21, a unique immunological adjuvant from Quillaja saponaria. Adv Exp Med Biol 1996;404:165-72
  • Kensil CR, Patel U, Lennick M, Marciani D. Separation and characterization of saponins with adjuvant activity from Quillaja-Saponaria Molina Cortex. J Immuno 1991;146:431-7
  • Kensil CR, Newman MJ, Coughlin RT, et al. The use of stimulon adjuvant to boost vaccine response. Vaccine Res 1993;2(4):273-81
  • Hancock GE, Speelman DJ, Frenchick PJ, et al. Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in Balb/c mice that are similar to those generated by experimental infection. Vaccine 1995;13(4):391-400
  • Meraldi V, Romero JF, Kensil C, et al. A strong CD8+ T cell response is elicited using the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei together with the adjuvant QS-21: quantitative and phenotypic comparison with the vaccine model of irradiated sporozoites. Vaccine 2005;23(21):2801-12
  • Sjolander S, Hansen JE, Lovgren-Bengtsson K, et al. Induction of homologous virus neutralizing antibodies in guinea-pigs immunized with two human immunodeficiency virus type 1 glycoprotein gp120-iscom preparations: a comparison with other adjuvant systems. Vaccine 1996;14(4):344-52
  • Evans TG, McElrath MJ, Matthews T, et al. QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. Vaccine 2001;19(15-16):2080-91
  • Moreno CA, Rodriguez R, Oliveira GA, et al. Preclinical evaluation of a synthetic Plasmodium falciparum MAP malaria vaccine in Aotus monkeys and mice. Vaccine 2000;18(1-2):89-99
  • Kashala O, Amador R, Valero MV, et al. Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant QS-21. Vaccine 2002;20(17-18):2263-77
  • Mbawuike I, Zang Y, Couch RB. Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant. Vaccine 2007;25(17):3263-9
  • Leroux-Roelsa G, Van Belleb P, Vandepapeliere P, et al. Vaccine Adjuvant Systems containing monophosphoryl lipid A andQS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination. Vaccine 2015;33(8):1084-91
  • Borja-Cabrera GP, Cruz Mendes A, Paraguai de Souza E, et al. Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine. Vaccine 2004;22(17–18):2234-43
  • da Silva BP, Correa Soares JB, Paraguai de Souza E, et al. Pulcherrima saponin, from the leaves of Calliandra pulcherrima, as adjuvant for immunization in the murine model of visceral leishmaniasis. Vaccine 2005;23(8):1061-71
  • Oliveira-Freitas E, Casas CP, Borja-Cabrera GP, et al. Acylated and deacylated saponins of Quillaja saponaria mixture as adjuvants for the FML-vaccine against visceral leishmaniasis. Vaccine 2006;24(18):3909-20
  • Livingston PO, Adluri S, Helling F, et al. Phase I trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. Vaccine 1994;12(14):1275-80
  • Ragupathi G, Livingston PO, Hood C, et al. Consistent antibody response against ganglioside GD2 induced in patients with melanoma by a GD2 lactone-keyhole limpet hemocyanin conjugate vaccine plus immunological adjuvant QS-21. Clin Cancer Res 2003;9(14):5214-20
  • Gilewski T, Ragupathi G, Bhuta S, et al. Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a Phase I trial. Proc Natl Acad Sci USA 2001;98(6):3270-5
  • Gilewski TA, Ragupathi G, Dickler M, et al. Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21. Clin Cancer Res 2007;13(10):2977-85
  • Huang YL, Hung JT, Cheung S, et al. Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc Nat Acad Sci USA 2013;110(7):2517-22
  • Slovin SF, Ragupathi G, Fernandez C, et al. A polyvalent vaccine for high-risk prostate patients: ‘are more antigens better?’ Cancer Immunol Immunother 2007;56(12):1921-30
  • Slovin SF, Ragupathi G, Musselli C, et al. Thomsen–Friedenreich (TF) antigen as a target for prostate cancer vaccine: clinical trial results with TF cluster (c)-KLH plus QS21 conjugate vaccine in patients with biochemically relapsed prostate cancer. Cancer Immunol Immunother 2005;54(7):694-702
  • Slovin SF, Ragupathi G, Musselli C, et al. Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with α-N-acetylgalactosamine-Oserine/threonine conjugate vaccine. J Clin Oncol 2003;21(23):4292-8
  • Dickler MN, Ragupathi G, Liu NX, et al. Immunogenicity of a fucosyl-GM1-keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer. Clin Cancer Res 1999;5(10):2773-9
  • Krug LM, Ragupathi G, Hood C, et al. Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin Cancer Res 2004;10(18 Pt 1):6094-100
  • Krug LM, Ragupathi G, Ng KK, et al. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res 2004;10(3):916-23
  • Sabbatini PJ, Ragupathi G, Hood C, et al. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer. Clin Cancer Res 2007;13(14):4170-7
  • Jacobsen NE, Fairbrother WJ, Kensil CR, et al. Structure of the saponin adjuvant QS-21 and its base-catalyzed isomerization product by H-1 and natural abundance C-13 NMR spectroscopy. Carbohydr Res 1996;280(1):1-14
  • Kensil CR. Saponins as vaccine adjuvants. Crit Rev Ther Drug Carr Syst 1996;13:1-55
  • Drane D, Gittleson C, Boyle J, et al. ISCOMATRIX™ adjuvant for prophylactic and therapeutic vaccines. Expert Rev Vaccines 2007;6(5):761-72
  • Ragupathi G, Gardner JR, Livingston PO, Gin DY. Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer. Expert Rev Vaccines 2011;10(4):463-70
  • Wikman M, Friedman M, Pinitkiatisakul S, et al. Achieving directed immunostimulating complexes incorporation. Expert Rev Vaccines 2006;5(3):395-403
  • Martín R, Briones R. Industrial uses and sustainable supply of Quillaja saponaria (rosaceae) saponins. Econ Bot 1999;53(3):302-11
  • Kim YJ, Wang P, Navarro-Villalobos M, et al. Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis of the potent clinical immune adjuvant QS-21Aapi. J Am Chem Soc 2006;128(36):11906-15
  • Wang P, Kim YJ, Navarro-Villalobos M, et al. Synthesis of the potent immunostimulatory adjuvant QS-21A. J Am Chem Soc 2005;127(10):3256-7
  • Deng K, Adams MM, Damani P, et al. Synthesis of QS-21-xylose: establishment of the immunopotentiating activity of synthetic QS-21 adjuvant with a melanoma vaccine. Angew Chem Int Ed Engl 2008;47(34):6395-8
  • Adams MM, Damani P, Perl NR, et al. Design and synthesis of potent quillaja saponin vaccine adjuvants. J Am Chem Soc 2010;132(6):1939-45
  • Marciani DJ, Reynolds RC, Pathak AK, et al. Fractionation, structural studies, and immunological characterization of the semi-synthetic Quillaja saponins derivative GPI-0100. Vaccine 2003;21(25–26):3961-71
  • Quenelle DC, Collins DJ, Marciani DJ, et al. Effect of immunization with herpes simplex virus type-1 (HSV-1) glycoprotein D (gD) plus the immune enhancer GPI-0100 on infection with HSV-1 or HSV-2. Vaccine 2006;24(10):1515-22
  • Quenelle DC, Collins DJ, Rice TL, et al. Effect of an immune enhancer, GPI-0100, on vaccination with live attenuated herpes simplex virus (HSV) type 2 or glycoprotein D on genital HSV-2 infections of guinea pigs. Antiviral Res 2008;80(2):223-4
  • Sun HX, Xie Y, Ye YP. Advances in saponin-based adjuvants. Vaccine 2009;27(12):1787-96
  • Chea EK, Fernández-Tejada A, Damani P, et al. Synthesis and preclinical evaluation of QS-21 variants leading to simplified vaccine adjuvants and mechanistic probes. J Am Chem Soc 2012;134(32):13448-57
  • Fernández-Tejada A, Chea EK, George C, et al. Development of a saponin vaccine adjuvant based on QS-21. Nat Chem 2014;6(7):635-43
  • Barclay T, Ginic-Markovic M, Cooper P, Petrovsky N. Inulin - a versatile polysaccharide with multiple pharmaceutical and food chemical uses. J Excipients Food Chem 2010;1(3):27-50
  • Cooper PD, Barclay TG, Ginic-Markovic M, Petrovsky N. The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions. Glycobiology 2013;23(10):1164-74
  • Hinrichs WL, Prinsen MG, Frijlink HW. Inulin glasses for the stabilization of therapeutic proteins. Int J Pharm 2001;215(1-2):163-74
  • Audouy SA, van der Schaaf G, Hinrichs WL, et al. Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization. Vaccine 2011;29(26):4345-52
  • de Jonge J, Amorij JP, Hinrichs WL, et al. Inulin sugar glasses preserve the structural integrity and biological activity of influenza virosomes during freeze-drying and storage. Eur J Pharm Sci 2007;32(1):33-44
  • Cooper PD. Vaccine adjuvants based on gamma inulin. Pharm Biotechnol 1995;6:559-80
  • Cooper PD, Steele EJ. The adjuvanticity of gamma inulin. Immunol Cell Biol 1988;66(Pt5-6):345-52
  • Cooper PD, Turner R, McGovern J. Algammulin (gamma inulin/alum hybrid adjuvant) has greater adjuvanticity than alum for hepatitis B surface antigen in mice. Immunol Lett 1991;27(2):131-4
  • Petrovsky N. Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity. Vaccine 2006;24(Suppl 2):26-9
  • Jones GL, Spencer L, Lord R, et al. Peptide vaccines derived from a malarial surface antigen: effects of dose and adjuvants on immunogenicity. Immunol Lett 1990;24(4):253-60
  • Frazer I, Tindle R, Fernando G, et al. Safety and immunogenicity of HPV16 E7/Algammulin. In: Tindle RW, editor. Vaccines for human papillomavirus infection and anogenital disease. RG Landes; New York: 1999. p. 91-104
  • Silva DG, Cooper PD, Petrovsky N. Inulin-derived adjuvants efficiently promote both Th1 and Th2 immune responses. Immunol Cell Biol 2004;82(6):611-16
  • Cooper PD, Carter M. The anti-melanoma activity of inulin in mice. Mol Immunol 1986;23(8):903-8
  • Korbelik M, Cooper PD. Potentiation of photodynamic therapy of cancer by complement: The effect of gamma-inulin. Br J Cancer 2007;96(1):67-72
  • Cooper PD, Petrovsky N. Delta inulin: a novel, immunologically active, stable packing structure comprising beta-D-[2→1] poly(fructo-furanosyl) alpha-D-glucose polymers. Glycobiology 2011;21(5):595-606
  • Lobigs M, Pavy M, Hall RA, et al. An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses. J Gen Virol 2010;91(Pt 6):1407-17
  • Cristillo AD, Ferrari MG, Hudacik L, et al. Induction of mucosal and systemic antibody and T-cell responses following primeboost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine formulations. J Gen Virol 2011;92(Pt 1):128-40
  • Honda-Okubo Y, Saade F, Petrovsky N. Advax, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine 2012;30(36):5373-81
  • Gordon DL, Sajkov D, Woodman RJ, et al. Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax polysaccharide adjuvant. Vaccine 2012;30(36):5407-16
  • Petrovsky N, Larena M, Siddharthan V, et al. An inactivated cell culture Japanese encephalitis vaccine (JE-ADVAX) formulated with delta inulin adjuvant provides robust heterologous protection against West Nile encephalitis via cross-protective memory B cells and neutralizing antibody. J Virol 2013;87(18):10324-33
  • Eckersley AM, Petrovsky N, Kinne J, et al. Improving the dromedary antibody response: The hunt for the ideal camel adjuvant. J Camel Pract And Res 2011;18(1):35-46
  • Saade F, Honda-Okubo Y, Trec S, Petrovsky N. A novel hepatitis B vaccine containing Advax, a polysaccharide adjuvant derived from delta inulin, induces robust humoral and cellular immunity with minimal reactogenicity in preclinical testing. Vaccine 2013;31(15):1999-2007
  • Rio E, Marradi M, Calderon-Gonzalez R, et al. A gold glyco-nanoparticle carrying a listeriolysin O peptide and formulated with AdvaxTM delta inulin adjuvant induces robust T-cell protection against listeria infection. Vaccine 2015;33(12):1465-73
  • Gordon D, Kelley P, Heinzel S, et al. Immunogenicity and safety of AdvaxTM, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: A randomized controlled Phase I study. Vaccine 2014;32(48):6469-77
  • Feinen B, Petrovsky N, Verma A, et al. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide djuvant. Clin Vaccine Immunol 2014;21(4):580-6
  • Cooper PD, Carter M. Anti-complementary action of polymorphic ‘solubility forms’ of particulate inulin. Mol Immunol 1986;23(8):895-901
  • Kumar S, Tummala H. Development of soluble inulin particles as a potent and safe vaccine adjuvant and delivery system. Mol Pharmceutics 2013;10(5):1845-53

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