Skip to main content
SpringerLink
Log in

Sugar-Based Immune Adjuvants for Use in Recombinant, Viral Vector, DNA and Other Styles of Vaccines

  • Chapter
  • First Online:
Novel Technologies for Vaccine Development

  • 1203 Accesses

Abstract

Highly attenuated viral vectors, purified protein antigens and DNA vaccines all suffer from problems of low immunogenicity providing a major challenge to find the best way to address this problem. A convenient solution is to identify a suitable adjuvant to add to the vaccine formulation to enhance its immunogenicity. Adjuvants come in many shapes and flavours, with no single unifying theme to explain why such a diversity of compounds should share the ability to enhance vaccine action. Hence adjuvant selection remains an empiric exercise of trial and error, largely based on comparisons of adjuvant potency in animal models plus assessment of safety and tolerability. In addition, there are unique challenges with successfully adjuvanting nonprotein-based vaccine technologies such as viral vectors or DNA vaccines for which existing adjuvant technologies such as aluminium salts or oil emulsions are likely to be unsuitable or incompatible. Amongst the many different groups of potential adjuvant compounds, carbohydrate-based adjuvants have received relatively little attention despite having favourable properties including compatibility for formulation with live vector vaccines, safety, tolerability and ease of manufacture and formulation. These properties may make them ideal for use across all vaccine platforms including live viral vectors and DNA vaccines. This chapter will review the various carbohydrate-based adjuvants and the science that underpins their activity and will highlight the potential for sugar-based adjuvants to replace more traditional adjuvant such as aluminium salts and oil emulsions across a wide variety of human and veterinary vaccine applications using traditional antigens, viral vectors or DNA to protect against infectious disease and for treatment of cancer and allergy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ara Y, Saito T, Takagi T, Hagiwara E, Miyagi Y, Sugiyama M, Kawamoto S, Ishii N, Yoshida T, Hanashi D, Koshino T, Okada H, Okuda K (2001) Zymosan enhances the immune response to DNA vaccine for human immunodeficiency virus type-1 through the activation of complement system. Immunology 103(1):98–105

    PubMed Central  PubMed  CAS  Google Scholar 

  • Arca HC, Gunbeyaz M, Senel S (2009) Chitosan-based systems for the delivery of vaccine antigens. Expert Rev Vaccines 8(7):937–953

    PubMed  CAS  Google Scholar 

  • Archambault D, Morin G, Elazhary Y (1988) Influence of immunomodulatory agents on bovine humoral and cellular immune responses to parenteral inoculation with bovine rotavirus vaccines. Vet Microbiol 17(4):323–334

    PubMed  CAS  Google Scholar 

  • Azuma I, Okumura H, Saiki I, Kiso M, Hasegawa A, Tanio Y, Yamamura Y (1981) Adjuvant activity of carbohydrate analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine in guinea pigs. Infect Immun 33(3):834–839

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bachelder EM, Beaudette TT, Broaders KE, Frechet JM, Albrecht MT, Mateczun AJ, Ainslie KM, Pesce JT, Keane-Myers AM (2010) In vitro analysis of acetalated dextran microparticles as a potent delivery platform for vaccine adjuvants. Mol Pharm 7(3):826–835

    PubMed Central  PubMed  CAS  Google Scholar 

  • Baudner BC, Giuliani MM, Verhoef JC, Rappuoli R, Junginger HE, Giudice GD (2003) The concomitant use of the LTK63 mucosal adjuvant and of chitosan-based delivery system enhances the immunogenicity and efficacy of intranasally administered vaccines. Vaccine 21(25–26):3837–3844

    PubMed  CAS  Google Scholar 

  • Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z (2004) Cell signals transduced by complement. Mol Immunol 41(6–7):583–597

    PubMed  CAS  Google Scholar 

  • Borges O, Cordeiro-da-Silva A, Tavares J, Santarem N, de Sousa A, Borchard G, Junginger HE (2008) Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles. Eur J Pharm Biopharm 69(2):405–416

    PubMed  CAS  Google Scholar 

  • Cekic C, Casella CR, Eaves CA, Matsuzawa A, Ichijo H, Mitchell TC (2009) Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A. J Biol Chem 284(46):31982–31991

    PubMed Central  PubMed  CAS  Google Scholar 

  • Chang H, Li X, Teng Y, Liang Y, Peng B, Fang F, Chen Z (2010) Comparison of adjuvant efficacy of chitosan and aluminum hydroxide for intraperitoneally administered inactivated influenza H5N1 vaccine. DNA Cell Biol 29(9):563–568

    PubMed  CAS  Google Scholar 

  • Chihara G, Hamuro J, Maeda YY, Shiio T, Suga T, Takasuka N, Sasaki T (1987) Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator: an overview. Cancer Detect Prev Suppl 1:423–443

    PubMed  CAS  Google Scholar 

  • Cooper PD, Carter M (1986) Anti-complementary action of polymorphic “solubility forms” of particulate inulin. Mol Immunol 23(8):895–901

    PubMed  CAS  Google Scholar 

  • Cooper PD, Petrovsky N (2011) Delta inulin: a novel, immunologically active, stable packing structure comprising beta-D-[2 -> 1] poly(fructo-furanosyl) alpha-D-glucose polymers. Glycobiology 21(5):595–606

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cooper PD, Barclay TG, Ginic-Markovic M, Petrovsky N (2013) The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions. Glycobiology 23(10):1164–1174

    PubMed Central  PubMed  CAS  Google Scholar 

  • Cristillo AD, Ferrari MG, Hudacik L, Lewis B, Galmin L, Bowen B, Thompson D, Petrovsky N, Markham P, Pal R (2011) Induction of mucosal and systemic antibody and T-cell responses following prime-boost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine formulations. J Gen Virol 92(Pt 1):128–140

    PubMed Central  PubMed  CAS  Google Scholar 

  • Dai JH, Iwatani Y, Ishida T, Terunuma H, Kasai H, Iwakula Y, Fujiwara H, Ito M (2001) Glycyrrhizin enhances interleukin-12 production in peritoneal macrophages. Immunology 103(2):235–243

    PubMed Central  PubMed  CAS  Google Scholar 

  • Deng K, Adams MM, Damani P, Livingston PO, Ragupathi G, Gin DY (2008) Synthesis of QS-21-xylose: establishment of the immunopotentiating activity of synthetic QS-21 adjuvant with a melanoma vaccine. Angew Chem Int Ed Engl 47(34):6395–6398

    PubMed Central  PubMed  CAS  Google Scholar 

  • Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, Kasprowicz DJ, Kellar K, Pare J, van Dyke T, Ziegler S, Unutmaz D, Pulendran B (2006) Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest 116(4):916–928

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ding ZY, Wang C, Su JM, Wei YQ, Wang CT (2009) A novel strategy for development of universal tumor vaccine: a DC-targeted adenovirus encoding hTRT. Sichuan Da Xue Xue Bao Yi Xue Ban 40(3):369–373

    PubMed  CAS  Google Scholar 

  • Dong SF, Chen JM, Zhang W, Sun SH, Wang J, Gu JX, Boraschi D, Qu D (2007) Specific immune response to HBsAg is enhanced by beta-glucan oligosaccharide containing an alpha-(1–>3)-linked bond and biased towards M2/Th2. Int Immunopharmacol 7(6):725–733

    PubMed  CAS  Google Scholar 

  • Doz E, Rose S, Nigou J, Gilleron M, Puzo G, Erard F, Ryffel B, Quesniaux VF (2007) Acylation determines the toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan. J Biol Chem 282(36):26014–26025

    PubMed  CAS  Google Scholar 

  • Drandarska I, Kussovski V, Nikolaeva S, Markova N (2005) Combined immunomodulating effects of BCG and Lentinan after intranasal application in guinea pigs. Int Immunopharmacol 5(4):795–803

    PubMed  CAS  Google Scholar 

  • Eckersley AM, Petrovsky N, Kinne J, Wernery R, Wernery U (2011) Improving the dromedary antibody response: the hunt for the ideal camel adjuvant. J Camel Pract Res 18(1):35–46

    Google Scholar 

  • El-Kamary SS, Pasetti MF, Mendelman PM, Frey SE, Bernstein DI, Treanor JJ, Ferreira J, Chen WH, Sublett R, Richardson C, Bargatze RF, Sztein MB, Tacket CO (2010) Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues. J Infect Dis 202(11):1649–1658

    PubMed Central  PubMed  CAS  Google Scholar 

  • Emod J, Joo I (1990) Nonspecific resistance-enhancing activity of zymosan in experimental bacterial infections. Acta Microbiol Hung 37(2):187–192

    PubMed  CAS  Google Scholar 

  • Fujita Y, Okamoto Y, Uenishi Y, Sunagawa M, Uchiyama T, Yano I (2007) Molecular and supra-molecular structure related differences in toxicity and granulomatogenic activity of mycobacterial cord factor in mice. Microb Pathog 43(1):10–21

    PubMed  CAS  Google Scholar 

  • Gauntt CJ, Wood HJ, McDaniel HR, McAnalley BH (2000) Aloe polymannose enhances anti-coxsackievirus antibody titres in mice. Phytother Res 14(4):261–266

    PubMed  CAS  Google Scholar 

  • Ghendon Y, Markushin S, Vasiliev Y, Akopova I, Koptiaeva I, Krivtsov G, Borisova O, Ahmatova N, Kurbatova E, Mazurina S, Gervazieva V (2009) Evaluation of properties of chitosan as an adjuvant for inactivated influenza vaccines administered parenterally. J Med Virol 81(3):494–506

    PubMed  CAS  Google Scholar 

  • Gogev S, de Fays K, Versali MF, Gautier S, Thiry E (2004) Glycol chitosan improves the efficacy of intranasally administrated replication defective human adenovirus type 5 expressing glycoprotein D of bovine herpesvirus 1. Vaccine 22(15–16):1946–1953

    PubMed  CAS  Google Scholar 

  • Gordon DL, Sajkov D, Woodman RJ, Honda-Okubo Y, Cox MM, Heinzel S, Petrovsky N (2012) Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax polysaccharide adjuvant. Vaccine 30(36):5407–5416

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Geijtenbeek TB (2009) Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol 10(10):1081–1088

    PubMed  CAS  Google Scholar 

  • Guo Z, Hu Y, Wang D, Ma X, Zhao X, Zhao B, Wang J, Liu P (2009) Sulfated modification can enhance the adjuvanticity of lentinan and improve the immune effect of ND vaccine. Vaccine 27(5):660–665

    PubMed  CAS  Google Scholar 

  • Hamasur B, Haile M, Pawlowski A, Schroder U, Williams A, Hatch G, Hall G, Marsh P, Kallenius G, Svenson SB (2003) Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis. Vaccine 21(25–26):4081–4093

    PubMed  CAS  Google Scholar 

  • Hida S, Nagi-Miura N, Adachi Y, Ohno N (2006) Beta-glucan derived from zymosan acts as an adjuvant for collagen-induced arthritis. Microbiol Immunol 50(6):453–461

    PubMed  CAS  Google Scholar 

  • Honda-Okubo Y, Saade F, Petrovsky N (2012) Advax, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine 30(36):5373–5381

    PubMed Central  PubMed  CAS  Google Scholar 

  • Houston WE, Crabbs CL, Kremer RJ, Springer JW (1976) Adjuvant effects of diethylaminoethyl-dextran. Infect Immun 13(6):1559–1562

    PubMed Central  PubMed  CAS  Google Scholar 

  • Huang H, Ostroff GR, Lee CK, Wang JP, Specht CA, Levitz SM (2009) Distinct patterns of dendritic cell cytokine release stimulated by fungal beta-glucans and toll-like receptor agonists. Infect Immun 77(5):1774–1781

    PubMed Central  PubMed  CAS  Google Scholar 

  • Huang H, Ostroff GR, Lee CK, Specht CA, Levitz SM (2010) Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded beta-glucan particles. MBio 1(3):e00164-10

    PubMed Central  PubMed  Google Scholar 

  • Irinoda K, Masihi KN, Chihara G, Kaneko Y, Katori T (1992) Stimulation of microbicidal host defence mechanisms against aerosol influenza virus infection by lentinan. Int J Immunopharmacol 14(6):971–977

    PubMed  CAS  Google Scholar 

  • Jackson EM, Herbst-Kralovetz MM (2012) Intranasal vaccination with murabutide enhances humoral and mucosal immune responses to a virus-like particle vaccine. PLoS One 7(7):e41529

    PubMed Central  PubMed  CAS  Google Scholar 

  • Jain S, Vyas SP (2005) Mannosylated niosomes as carrier adjuvant system for topical immunization. J Pharm Pharmacol 57(9):1177–1184

    PubMed  CAS  Google Scholar 

  • Jain S, Singh P, Mishra V, Vyas SP (2005) Mannosylated niosomes as adjuvant-carrier system for oral genetic immunization against hepatitis B. Immunol Lett 101(1):41–49

    PubMed  CAS  Google Scholar 

  • Jeannin JF, Lagadec P, Pelletier H, Reisser D, Olsson NO, Chihara G, Martin F (1988) Regression induced by lentinan, of peritoneal carcinomatoses in a model of colon cancer in rat. Int J Immunopharmacol 10(7):855–861

    PubMed  CAS  Google Scholar 

  • Kaistha J, Sokhey J, Singh S, Kumar S, John PC, Sharma NC (1996) Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated phenol preserved typhoid vaccine. Indian J Pathol Microbiol 39(4):287–292

    PubMed  CAS  Google Scholar 

  • Katsara M, Yuriev E, Ramsland PA, Tselios T, Deraos G, Lourbopoulos A, Grigoriadis N, Matsoukas J, Apostolopoulos V (2009) Altered peptide ligands of myelin basic protein (MBP87–99) conjugated to reduced mannan modulate immune responses in mice. Immunology 128(4):521–533

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kawakami S, Sato A, Nishikawa M, Yamashita F, Hashida M (2000) Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes. Gene Ther 7(4):292–299

    PubMed  CAS  Google Scholar 

  • Kawasaki A, Takada H, Kotani S, Inai S, Nagaki K, Matsumoto M, Yokogawa K, Kawata S, Kusumoto S, Shiba T (1987) Activation of the human complement cascade by bacterial cell walls, peptidoglycans, water-soluble peptidoglycan components, and synthetic muramylpeptides–studies on active components and structural requirements. Microbiol Immunol 31(6):551–569

    PubMed  CAS  Google Scholar 

  • Kensil CR, Wu JY, Soltysik S (1995) Structural and immunological characterization of the vaccine adjuvant QS-21. Pharm Biotechnol 6:525–541

    PubMed  CAS  Google Scholar 

  • Kensil CR, Soltysik S, Wheeler DA, Wu JY (1996) Structure/function studies on QS-21, a unique immunological adjuvant from Quillaja saponaria. Adv Exp Med Biol 404:165–172

    PubMed  CAS  Google Scholar 

  • Khatri K, Goyal AK, Gupta PN, Mishra N, Vyas SP (2008) Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Int J Pharm 354(1–2):235–241

    PubMed  CAS  Google Scholar 

  • Koike Y, Yoo YC, Mitobe M, Oka T, Okuma K, Tono-oka S, Azuma I (1998) Enhancing activity of mycobacterial cell-derived adjuvants on immunogenicity of recombinant human hepatitis B virus vaccine. Vaccine 16(20):1982–1989

    PubMed  CAS  Google Scholar 

  • Kotze AF, Luessen HL, de Leeuw BJ, de Boer BG, Verhoef JC, Junginger HE (1997) N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: in vitro evaluation in intestinal epithelial cells (Caco-2). Pharm Res 14(9):1197–1202

    PubMed  CAS  Google Scholar 

  • Lacaille-Dubois M-A, Atta ur R (2005) Bioactive saponins with cancer related and immunomodulatory activity: recent developments. Stud Nat Prod Chem 32:209–246

    CAS  Google Scholar 

  • Lameiro MH, Malpique R, Silva AC, Alves PM, Melo E (2006) Encapsulation of adenoviral vectors into chitosan-bile salt microparticles for mucosal vaccination. J Biotechnol 126(2):152–162

    PubMed  CAS  Google Scholar 

  • Lamkanfi M, Malireddi RK, Kanneganti TD (2009) Fungal zymosan and mannan activate the cryopyrin inflammasome. J Biol Chem 284(31):20574–20581

    PubMed Central  PubMed  CAS  Google Scholar 

  • Larena M, Prow NA, Hall RA, Petrovsky N, Lobigs M (2013) JE-ADVAX vaccine protection against Japanese encephalitis mediated by memory B cells in the absence of CD8+ T cells and pre-exposure neutralizing antibody. J Virol 87(8):4395–4402

    PubMed Central  PubMed  CAS  Google Scholar 

  • Layton RC, Petrovsky N, Gigliotti AP, Pollock Z, Knight J, Donart N, Pyles J, Harrod KS, Gao P, Koster F (2011) Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1 vaccine to protect against lethal challenge in ferrets. Vaccine 29(37):6242–6251

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK (2001) Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int Immunopharmacol 1(7):1275–1284

    PubMed  CAS  Google Scholar 

  • Lemke CD, Graham JB, Geary SM, Zamba G, Lubaroff DM, Salem AK (2011) Chitosan is a surprising negative modulator of cytotoxic CD8+ T cell responses elicited by adenovirus cancer vaccines. Mol Pharm 8(5):1652–1661

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lobigs M, Pavy M, Hall RA, Lobigs P, Cooper P, Komiya T, Toriniwa H, Petrovsky N (2010) 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 91(Pt 6):1407–1417

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lu Y, Kawakami S, Yamashita F, Hashida M (2007) Development of an antigen-presenting cell-targeted DNA vaccine against melanoma by mannosylated liposomes. Biomaterials 28(21):3255–3262

    PubMed  CAS  Google Scholar 

  • Marciani DJ, Press JB, Reynolds RC, Pathak AK, Pathak V, Gundy LE, Farmer JT, Koratich MS, May RD (2000) Development of semisynthetic triterpenoid saponin derivatives with immune stimulating activity. Vaccine 18(27):3141–3151

    PubMed  CAS  Google Scholar 

  • Masihi KN, Brehmer W, Lange W, Ribi E (1983) Effects of mycobacterial fractions and muramyl dipeptide on the resistance of mice to aerogenic influenza virus infection. Int J Immunopharmacol 5(5):403–410

    PubMed  CAS  Google Scholar 

  • Masihi KN, Lange W, Brehmer W, Ribi E (1986) Immunobiological activities of nontoxic lipid A: enhancement of nonspecific resistance in combination with trehalose dimycolate against viral infection and adjuvant effects. Int J Immunopharmacol 8(3):339–345

    PubMed  CAS  Google Scholar 

  • Meraldi V, Romero JF, Kensil C, Corradin G (2005) 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 23(21):2801–2812

    PubMed  CAS  Google Scholar 

  • Miller E, Andrews N, Stellitano L, Stowe J, Winstone AM, Shneerson J, Verity C (2013) Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ 346:f794

    PubMed  Google Scholar 

  • Mohagheghpour N, Dawson M, Hobbs P, Judd A, Winant R, Dousman L, Waldeck N, Hokama L, Tuse D, Kos F et al (1995) Glucans as immunological adjuvants. Adv Exp Med Biol 383:13–22

    PubMed  CAS  Google Scholar 

  • Morikawa K, Takeda R, Yamazaki M, Mizuno D (1985) Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1,3-D-glucan and other immunomodulators in murine cells. Cancer Res 45(4):1496–1501

    PubMed  CAS  Google Scholar 

  • Newman MJ, Wu JY, Gardner BH, Anderson CA, Kensil CR, Recchia J, Coughlin RT, Powell MF (1997) Induction of cross-reactive cytotoxic T-lymphocyte responses specific for HIV-1 gp120 using saponin adjuvant (QS-21) supplemented subunit vaccine formulations. Vaccine 15(9):1001–1007

    PubMed  CAS  Google Scholar 

  • Nishiyama A, Tsuji S, Yamashita M, Henriksen RA, Myrvik QN, Shibata Y (2006) Phagocytosis of N-acetyl-D-glucosamine particles, a Th1 adjuvant, by RAW 264.7 cells results in MAPK activation and TNF-alpha, but not IL-10, production. Cell Immunol 239(2):103–112

    PubMed  CAS  Google Scholar 

  • Ott G, Barchfeld GL, Van Nest G (1995) Enhancement of humoral response against human influenza vaccine with the simple submicron oil/water emulsion adjuvant MF59. Vaccine 13(16):1557–1562

    PubMed  CAS  Google Scholar 

  • Passeri E, Villa C, Couette M, Itti E, Brugieres P, Cesaro P, Gherardi RK, Bachoud-Levi AC, Authier FJ (2011) Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF). J Inorg Biochem 105(11):1457–1463

    PubMed  CAS  Google Scholar 

  • Petrovsky N (2008) Freeing vaccine adjuvants from dangerous immunological dogma. Expert Rev Vaccines 7(1):7–10

    PubMed  CAS  Google Scholar 

  • Petrovsky N (2013) Vaccine adjuvant safety: the elephant in the room. Expert Rev Vaccines 12(7):715–717

    PubMed  CAS  Google Scholar 

  • Petrovsky N, Aguilar JC (2004) Vaccine adjuvants: current state and future trends. Immunol Cell Biol 82(5):488–496

    PubMed  CAS  Google Scholar 

  • Petrovsky N, Larena M, Siddharthan V, Prow NA, Hall RA, Lobigs M, Morrey J (2013) 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 87(18):10324–10333

    PubMed Central  PubMed  CAS  Google Scholar 

  • Petrushina I, Ghochikyan A, Mkrtichyan M, Mamikonyan G, Movsesyan N, Ajdari R, Vasilevko V, Karapetyan A, Lees A, Agadjanyan MG, Cribbs DH (2008) Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice. J Neuroinflammation 5:42

    PubMed Central  PubMed  Google Scholar 

  • Pham HL, Ross BP, McGeary RP, Shaw PN, Hewavitharana AK, Davies NM (2006) Saponins from Quillaja saponaria Molina: isolation, characterization and ability to form immuno stimulatory complexes (ISCOMs). Curr Drug Deliv 3(4):389–397

    PubMed  CAS  Google Scholar 

  • Prego C, Paolicelli P, Diaz B, Vicente S, Sanchez A, Gonzalez-Fernandez A, Alonso MJ (2010) Chitosan-based nanoparticles for improving immunization against hepatitis B infection. Vaccine 28(14):2607–2614

    PubMed  CAS  Google Scholar 

  • Quan FS, Ko EJ, Kwon YM, Joo KH, Compans RW, Kang SM (2013) Mucosal adjuvants for influenza virus-like particle vaccine. Viral Immunol 26(6):385–395

    PubMed  CAS  Google Scholar 

  • Quenelle DC, Collins DJ, Rice TL, Prichard MN, Marciani DJ, Kern ER (2008) 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 80(2):223–224

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ragupathi G, Coltart DM, Williams LJ, Koide F, Kagan E, Allen J, Harris C, Glunz PW, Livingston PO, Danishefsky SJ (2002) On the power of chemical synthesis: immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc Natl Acad Sci U S A 99(21):13699–13704

    PubMed Central  PubMed  CAS  Google Scholar 

  • Raphael TJ, Kuttan G (2003) Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system. Phytomedicine 10(6–7):483–489

    PubMed  CAS  Google Scholar 

  • Rauw F, Gardin Y, Palya V, Anbari S, Lemaire S, Boschmans M, van den Berg T, Lambrecht B (2010) Improved vaccination against Newcastle disease by an in ovo recombinant HVT-ND combined with an adjuvanted live vaccine at day-old. Vaccine 28(3):823–833

    PubMed  CAS  Google Scholar 

  • Rawal N, Rajagopalan R, Salvi VP (2009) Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP). Mol Immunol 46(15):2902–2910

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ray TL, Hanson A, Ray LF, Wuepper KD (1979) Purification of a mannan from Candida albicans which activates serum complement. J Invest Dermatol 73(4):269–274

    PubMed  CAS  Google Scholar 

  • Ribi E, Meyer TJ, Azuma I, Parker R, Brehmer W (1975) Biologically active components from mycobacterial cell walls. IV. Protection of mice against aerosol infection with virulent mycobacterium tuberculosis. Cell Immunol 16(1):1–10

    PubMed  CAS  Google Scholar 

  • Ribi E, Granger DL, Milner KC, Yamamoto K, Strain SM, Parker R, Smith RW, Brehmer W, Azuma I (1982) Induction of resistance to tuberculosis in mice with defined components of Mycobacteria and with some unrelated materials. Zentralbl Bakteriol Mikrobiol Hyg A 251(3):345–356

    PubMed  CAS  Google Scholar 

  • Rojs OZ, Cerne M, Mrzel I, Urleb U, Muraoka S (2000) Immunostimulatory effects of the muramyl dipeptide analogue LK415 in chickens immunized with a vaccine strain of infectious bursal disease virus. Acta Vet Hung 48(2):237–248

    PubMed  CAS  Google Scholar 

  • Saade F, Honda-Okubo Y, Trec S, Petrovsky N (2013) 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 31(15):1999–2007

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sasaki S, Sumino K, Hamajima K, Fukushima J, Ishii N, Kawamoto S, Mohri H, Kensil CR, Okuda K (1998) Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes. J Virol 72(6):4931–4939

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sato M, Sano H, Iwaki D, Kudo K, Konishi M, Takahashi H, Takahashi T, Imaizumi H, Asai Y, Kuroki Y (2003) Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J Immunol 171(1):417–425

    PubMed  CAS  Google Scholar 

  • Schiller JT, Castellsague X, Villa LL, Hildesheim A (2008) An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 26(Suppl 10):K53–K61

    PubMed Central  PubMed  CAS  Google Scholar 

  • Schorlemmer HU, Bitter-Suermann D, Allison AC (1977) Complement activation by the alternative pathway and macrophage enzyme secretion in the pathogenesis of chronic inflammation. Immunology 32(6):929–940

    PubMed Central  PubMed  CAS  Google Scholar 

  • Schwarzkopf C, Thiele B (1996) Effectivity of alternative adjuvants in comparison to Freund’s complete adjuvant. ALTEX 13(5):22–25

    PubMed  Google Scholar 

  • Sheng KC, Pouniotis DS, Wright MD, Tang CK, Lazoura E, Pietersz GA, Apostolopoulos V (2006) Mannan derivatives induce phenotypic and functional maturation of mouse dendritic cells. Immunology 118(3):372–383

    PubMed Central  PubMed  CAS  Google Scholar 

  • Stambas J, Pietersz G, McKenzie I, Cheers C (2002) Oxidised mannan as a novel adjuvant inducing mucosal IgA production. Vaccine 20(7–8):1068–1078

    PubMed  CAS  Google Scholar 

  • Sueoka E, Nishiwaki S, Okabe S, Iida N, Suganuma M, Yano I, Aoki K, Fujiki H (1995) Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-alpha release in mouse lung tissues. Jpn J Cancer Res 86(8):749–755

    PubMed  CAS  Google Scholar 

  • Sun HX, Xie Y, Ye YP (2009) Advances in saponin-based adjuvants. Vaccine 27(12):1787–1796

    PubMed  CAS  Google Scholar 

  • Takada H, Uehara A (2006) Enhancement of TLR-mediated innate immune responses by peptidoglycans through NOD signaling. Curr Pharm Des 12(32):4163–4172

    PubMed  CAS  Google Scholar 

  • Takahara K, Yashima Y, Omatsu Y, Yoshida H, Kimura Y, Kang YS, Steinman RM, Park CG, Inaba K (2004) Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins. Int Immunol 16(6):819–829

    PubMed  CAS  Google Scholar 

  • Thiel S, Gadjeva M (2009) Humoral pattern recognition molecules: mannan-binding lectin and ficolins. Adv Exp Med Biol 653:58–73

    PubMed  CAS  Google Scholar 

  • Toda S, Ishii N, Okada E, Kusakabe KI, Arai H, Hamajima K, Gorai I, Nishioka K, Okuda K (1997) HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-gamma antibody. Immunology 92(1):111–117

    PubMed Central  PubMed  CAS  Google Scholar 

  • Tong NK, Beran J, Kee SA, Miguel JL, Sanchez C, Bayas JM, Vilella A, de Juanes JR, Arrazola P, Calbo-Torrecillas F, de Novales EL, Hamtiaux V, Lievens M, Stoffel M (2005) Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int 68(5):2298–2303

    PubMed  CAS  Google Scholar 

  • Uehara A, Yang S, Fujimoto Y, Fukase K, Kusumoto S, Shibata K, Sugawara S, Takada H (2005) Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture. Cell Microbiol 7(1):53–61

    PubMed  CAS  Google Scholar 

  • Valensi JP, Carlson JR, Van Nest GA (1994) Systemic cytokine profiles in BALB/c mice immunized with trivalent influenza vaccine containing MF59 oil emulsion and other advanced adjuvants. J Immunol 153(9):4029–4039

    PubMed  CAS  Google Scholar 

  • Vassilaros S, Tsibanis A, Tsikkinis A, Pietersz GA, McKenzie IF, Apostolopoulos V (2013) Up to 15-year clinical follow-up of a pilot Phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1. Immunotherapy 5(11):1177–1182

    PubMed  CAS  Google Scholar 

  • Vosika GJ, Cornelius DA, Bennek JA, Sadlik JR, Gilbert CW (1990) Immunologic and toxicologic study of disaccharide tripeptide glycerol dipalmitoyl: a new lipophilic immunomodulator. Mol Biother 2(1):50–56

    PubMed  CAS  Google Scholar 

  • Vosika GJ, Cornelius DA, Gilbert CW, Sadlik JR, Bennek JA, Doyle A, Hertsgaard D (1991) Phase I trial of ImmTher, a new liposome-incorporated lipophilic disaccharide tripeptide. J Immunother 10(4):256–266

    PubMed  CAS  Google Scholar 

  • Wang J, Zhou ZD, Xia DJ (2007) Study on effect of lentinan in enhancing anti-tumor action of dendritic cytoma vaccine and its mechanism. Zhongguo Zhong Xi Yi Jie He Za Zhi 27(1):60–64

    PubMed  Google Scholar 

  • Wang X, Zhang W, Liu F, Zheng M, Zheng D, Zhang T, Yi Y, Ding Y, Luo J, Dai C, Wang H, Sun B, Chen Z (2012) Intranasal immunization with live attenuated influenza vaccine plus chitosan as an adjuvant protects mice against homologous and heterologous virus challenge. Arch Virol 157(8):1451–1461

    PubMed  CAS  Google Scholar 

  • Weston SA, Parish CR (1991) Modification of lymphocyte migration by mannans and phosphomannans. Different carbohydrate structures control entry of lymphocytes into spleen and lymph nodes. J Immunol 146(12):4180–4186

    PubMed  CAS  Google Scholar 

  • Wierzbicki A, Kiszka I, Kaneko H, Kmieciak D, Wasik TJ, Gzyl J, Kaneko Y, Kozbor D (2002) Immunization strategies to augment oral vaccination with DNA and viral vectors expressing HIV envelope glycoprotein. Vaccine 20(9–10):1295–1307

    PubMed  CAS  Google Scholar 

  • Williams DL, Cook JA, Hoffmann EO, Di Luzio NR (1978) Protective effect of glucan in experimentally induced candidiasis. J Reticuloendothel Soc 23(6):479–490

    PubMed  CAS  Google Scholar 

  • Yamamura Y, Azuma I, Sugimura K, Yamawaki M, Uemiya M (1976) Adjuvant activity of 6-O-mycoloyl-N-acetylmuramuyl-L-alanyl-D-isoglutamine. Gann 67(6):867–877

    PubMed  CAS  Google Scholar 

  • Zhao Z, Yao Y, Ding Z, Chen X, Xie K, Luo Y, Zhang J, Chen X, Wu X, Xu J, Zhao J, Niu T, Liu J, Li Q, Zhang W, Wen Y, Su J, Hu B, Bu H, Wei Y, Wu Y (2011) Antitumour immunity mediated by mannan-modified adenovirus vectors expressing VE-cadherin. Vaccine 29(25):4218–4224

    PubMed  CAS  Google Scholar 

  • Zhao K, Chen G, Shi XM, Gao TT, Li W, Zhao Y, Zhang FQ, Wu J, Cui X, Wang YF (2012) Preparation and efficacy of a live newcastle disease virus vaccine encapsulated in chitosan nanoparticles. PLoS One 7(12):e53314

    PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Diabetes and Endocrinology, Flinders Medical Centre, Flinders University, Adelaide, 5042, SA, Australia

    Nikolai Petrovsky

  2. Vaxine Pty Ltd, Bedford Park, Adelaide, 5042, Australia

    Nikolai Petrovsky

Authors
  1. Nikolai Petrovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikolai Petrovsky .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Toxicolog Department of Microbiology and Immunolog, University of Louisville, Louisville, Kentucky, USA

    Igor S Lukashevich

  2. Department of Microbiology and Immunolog, University of Louisville, Louisville, Kentucky, USA

    Haval Shirwan

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Petrovsky, N. (2014). Sugar-Based Immune Adjuvants for Use in Recombinant, Viral Vector, DNA and Other Styles of Vaccines. In: Lukashevich, I., Shirwan, H. (eds) Novel Technologies for Vaccine Development. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1818-4_7

Download citation

Publish with us

Policies and ethics

Search

Navigation