Abstract
Vaccines have been one of the most important discoveries of modern medicine. They are the primary mode of protection against a wide range of infectious diseases and, if effective, can provide long-lasting immunity. Despite recent advances in our understanding of the immune system, prophylactic vaccines against chronic infectious diseases and immunotherapeutic vaccines against cancer remain elusive. Unlike preventive vaccines that have virtually eradicated fatal diseases like polio and smallpox, immunotherapy of chronic diseases and established or unexpected infections, for example human immunodeficiency virus (HIV), has yet to demonstrate global clinical success. Even for diseases where preventive vaccines are available, for example influenza, the protection is transient and requires multiple administration and yearly immunizations. In addition, most cancers and emerging infectious diseases, like the H1N1 influenza, and drug resistance infections like tuberculosis, need new transformative strategies to increase protective immunity many folds over currently available vaccines. Successful immunotherapy using vaccines requires effective strategies to penetrate tissue barriers, efficiently target antigens, adjuvants and immune-modulators to immune surveillance cells, provide strong stimulatory effects to activate those cells, and modulate the cellular response appropriately and efficiently in order to generate potent antiviral or anticancer immunity. The emerging field of immunobioengineering provides new concepts and strategies to design materials, antigens, and adjuvants to induce potent immune response; and engineer vaccine delivery systems to modulate the behavior of immune cells [1]. In this chapter we review the state-of-the-art approaches in immunobioengineering with specific focus on delivery formulations for multiple immune-modulators and antigens.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hubbell JA, Thomas SN, Swartz MA (2009) Materials engineering for immunomodulation. Nature 462(7272):449–460
Zhao X et al (2005) Directed cell migration via chemoattractants released from degradable microspheres. Biomaterials 26(24):5048–5063
Hart DN (1997) Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90(9):3245–3287
Viallard JF et al (1999) Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 115(1):189–195
Borrow P et al (1997) Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 3(2):205–211
Rinaldo C et al (1995) High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol 69(9):5838–5842
Malanchere-Bres E et al (2001) CpG oligodeoxynucleotides with hepatitis B surface antigen (HBsAg) for vaccination in HBsAg-transgenic mice. J Virol 75(14):6482–6491
Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383(6603):787–793
Roy K et al (1999) Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 5(4):387–391
Wild JS, Sur S (2001) CpG oligonucleotide modulation of allergic inflammation. Allergy 56(5):365–376
Goodman JS et al (1998) DNA immunotherapeutics: new potential treatment modalities for allergic disease. Int Arch Allergy Immunol 116(3):177–187
Gurunathan S, Klinman DM, Seder RA (2000) DNA vaccines: immunology, application, and optimization. Annu Rev Immunol 18:927–974
Donnelly JJ, Ulmer JB (1999) DNA vaccines for viral diseases. Braz J Med Biol Res 32(2):215–222
Calarota S et al (1998) Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 351(9112):1320–1325
O’Hagan D, Singh M, Ulmer J (2006) Microparticle-based technologies for vaccines. Methods 40:10–19
Kranzer K et al (2000) CpG-oligodeoxynucleotides enhance T-cell receptor-triggered interferon-gamma production and up-regulation of CD69 via induction of antigen-presenting cell-derived interferon type I and interleukin-12. Immunology 99(2):170–178
Shoda LK et al (2001) Immunostimulatory CpG-modified plasmid DNA enhances IL-12, TNF-alpha, and NO production by bovine macrophages. J Leukoc Biol 70(1):103–112
Heeg K, Zimmermann S (2000) CpG DNA as a Th1 trigger. Int Arch Allergy Immunol 121(2):87–97
Heeg K (2000) CpG DNA co-stimulates antigen-reactive T cells. Curr Top Microbiol Immunol 247:93–105
Davis HL (2000) Use of CpG DNA for enhancing specific immune responses. Curr Top Microbiol Immunol 247:171–183
McCluskie MJ, Weeratna RD, Davis HL (2000) The role of CpG in DNA vaccines. Springer Semin Immunopathol 22(1–2):125–132
Krieg AM, Davis HL (2001) Enhancing vaccines with immune stimulatory CpG DNA. Curr Opin Mol Ther 3(1):15–24
Manoj S, Babiuk LA, van Drunen Littel-van den Hurk S (2004) Approaches to enhance the efficacy of DNA vaccines. Crit Rev Clin Lab Sci 41(1):1–39
Boussif O et al (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 92(16):7297–7301
Neu M, Fischer D, Kissel T (2005) Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J Gene Med 7(8):992–1009
de Chastellier C, Thilo L (1997) Phagosome maturation and fusion with lysosomes in relation to surface property and size of the phagocytic particle. Eur J Cell Biol 74(1):49–62
Jilek S, Merkle HP, Walter E (2005) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliv Rev 57(3):377–390
Wagner E, Ogris M, Zauner W (1998) Polylysine-based transfection systems utilizing receptor-mediated delivery. Adv Drug Deliv Rev 30(1–3):97–113
Nguyen D et al (2008) Polymeric materials for gene delivery and DNA vaccination. Adv Mater 20:1–21
Regnstrom K et al (2003) PEI—a potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice. Gene Ther 10(18):1575–1583
Richardson SC, Kolbe HV, Duncan R (1999) Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA. Int J Pharm 178(2):231–243
Illum L et al (2001) Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev 51(1–3):81–96
Li GP et al (2009) Induction of Th1-type immune response by chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen Der p 2 for oral vaccination in mice. Cell Mol Immunol 6(1):45–50
Hedley ML, Curley J, Urban R (1998) Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nat Med 4(3):365–368
Klencke B et al (2002) Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101. Clin Cancer Res 8(5):1028–1037
Mathiowitz E et al (1997) Biologically erodable microspheres as potential oral drug delivery systems. Nature 386(6623):410–414
Wang D et al (2004) Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza virus hemagglutinin elicits mucosal, cellular and humoral immune responses. J Clin Virol 31(Suppl 1):S99–S106
Singh A et al (2008) Efficient modulation of T-cell response by dual-mode, single-carrier delivery of cytokine-targeted siRNA and DNA vaccine to antigen-presenting cells. Mol Ther 16(12):2011–2021
Little SR et al (2004) Poly-beta amino ester-containing microparticles enhance the activity of nonviral genetic vaccines. Proc Natl Acad Sci U S A 101(26):9534–9539
Hedley ML (2003) Formulations containing poly(lactide-co-glycolide) and plasmid DNA expression vectors. Expert Opin Biol Ther 3(6):903–910
Thiele L et al (2001) Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages? J Control Release 76(1–2):59–71
Thiele L, Merkle HP, Walter E (2003) Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages. Pharm Res 20(2):221–228
Kasturi SP et al (2011) Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470(7335):543–547
Singh M, Chakrapani A, O’Hagan D (2007) Nanoparticles and microparticles as vaccine-delivery systems. Expert Rev Vaccines 6(5):797–808
Vordermeier HM et al (1995) Synthetic delivery system for tuberculosis vaccines: immunological evaluation of the M. tuberculosis 38 kDa protein entrapped in biodegradable PLG microparticles. Vaccine 13(16):1576–1582
Luby TM et al (2004) Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1. Clin Immunol 112(1):45–53
Jung T et al (2001) Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice. Pharm Res 18(3):352–360
Newman KD, Samuel J, Kwon G (1998) Ovalbumin peptide encapsulated in poly(d, l Âlactic-co-glycolic acid) microspheres is capable of inducing a T helper type 1 immune response. J Control Release 54(1):49–59
Matzelle MM, Babensee JE (2004) Humoral immune responses to model antigen co-delivered with biomaterials used in tissue engineering. Biomaterials 25(2):295–304
Carcaboso AM et al (2004) Potent, long lasting systemic antibody levels and mixed Th1/Th2 immune response after nasal immunization with malaria antigen loaded PLGA microparticles. Vaccine 22(11–12):1423–1432
Kazzaz J et al (2006) Encapsulation of the immune potentiators MPL and RC529 in PLG microparticles enhances their potency. J Control Release 110(3):566–573
Diwan M, Tafaghodi M, Samuel J (2002) Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres. J Control Release 85(1–3):247–262
Tafaghodi M, Sajadi Tabassi SA, Jaafari MR (2006) Induction of systemic and mucosal immune responses by intranasal administration of alginate microspheres encapsulated with tetanus toxoid and CpG-ODN. Int J Pharm 319(1–2):37–43
Borges O et al (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
O’Hagan DT, Singh M, Ulmer JB (2004) Microparticles for the delivery of DNA vaccines. Immunol Rev 199:191–200
Denis-Mize KS et al (2000) Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells. Gene Ther 7(24):2105–2112
Singh M, O’Hagan D (1999) Advances in vaccine adjuvants. Nat Biotechnol 17(11):1075–1081
Singh M et al (2001) Cationic microparticles are an effective delivery system for immune stimulatory cpG DNA. Pharm Res 18(10):1476–1479
Kasturi SP, Sachaphibulkij K, Roy K (2005) Covalent conjugation of polyethyleneimine on biodegradable microparticles for delivery of plasmid DNA vaccines. Biomaterials 26(32):6375–6385
Pai Kasturi S et al (2006) Prophylactic anti-tumor effects in a B cell lymphoma model with DNA vaccines delivered on polyethylenimine (PEI) functionalized PLGA microparticles. J Control Release 113(3):261–270
Singh M et al (2000) Cationic microparticles: a potent delivery system for DNA vaccines. Proc Natl Acad Sci U S A 97(2):811–816
Luo Y et al (2003) Plasmid DNA encoding human carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA-transgenic mice. Vaccine 21(17–18):1938–1947
Mollenkopf HJ et al (2004) Enhanced protective efficacy of a tuberculosis DNA vaccine by adsorption onto cationic PLG microparticles. Vaccine 22(21–22):2690–2695
He X et al (2005) Augmented humoral and cellular immune responses to hepatitis B DNA vaccine adsorbed onto cationic microparticles. J Control Release 107(2):357–372
Oster CG et al (2005) Cationic microparticles consisting of poly(lactide-co-glycolide) and polyethylenimine as carriers systems for parental DNA vaccination. J Control Release 104(2):359–377
Jaganathan KS, Vyas SP (2006) Strong systemic and mucosal immune responses to surface-modified PLGA microspheres containing recombinant hepatitis B antigen administered intranasally. Vaccine 24(19):4201–4211
Fay F et al (2010) Gene delivery using dimethyldidodecylammonium bromide-coated PLGA nanoparticles. Biomaterials 31(14):4214–4222
Walter E, Merkle HP (2002) Microparticle-mediated transfection of non-phagocytic cells in vitro. J Drug Target 10(1):11–21
Kazzaz J et al (2000) Novel anionic microparticles are a potent adjuvant for the induction of cytotoxic T lymphocytes against recombinant p55 gag from HIV-1. J Control Release 67:347–356
Singh M et al (2004) Anionic microparticles are a potent delivery system for recombinant antigens from Neisseria meningitidis serotype B. J Pharm Sci 93(2):273–282
Wendorf J et al (2008) A comparison of anionic nanoparticles and microparticles as vaccine delivery systems. Hum Vaccin 4(1):44–49
Ataman-Onal Y et al (2006) Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models. J Control Release 112:175–185
O’Hagan DT, Valiante NM (2003) Recent advances in the discovery and delivery of vaccine adjuvants. Nat Rev Drug Discov 2(9):727–735
Singh M, O’Hagan DT (2002) Recent advances in vaccine adjuvants. Pharm Res 19(6):715–728
Zhao Z, Leong KW (1996) Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci 85(12):1261–1270
O’Hagan DT, Ott GS, Van Nest G (1997) Recent advances in vaccine adjuvants: the development of MF59 emulsion and polymeric microparticles. Mol Med Today 3(2):69–75
Kenney RT, Edelman R (2003) Survey of human-use adjuvants. Expert Rev Vaccines 2(2):167–188
Relyveld EH, Bizzini B, Gupta RK (1998) Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids. Vaccine 16(9–10):1016–1023
Ulanova M et al (2001) The Common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun 69(2):1151–1159
Mutwiri G et al (2008) Co-administration of polyphosphazenes with CpG oligodeoxynucleotides strongly enhances immune responses in mice immunized with Hepatitis B virus surface antigen. Vaccine 26(22):2680–2688
Woo SJ et al (2008) Co-administration of carcinoembryonic antigen and HIV TAT fusion protein with CpG-oligodeoxynucleotide induces potent antitumor immunity. Cancer Sci 99(5):1034–1039
Malyala P, O’Hagan DT, Singh M (2009) Enhancing the therapeutic efficacy of CpG oligonucleotides using biodegradable microparticles. Adv Drug Deliv Rev 61(3):218–225
Vandepapeliere P et al (2008) Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers. Vaccine 26(10):1375–1386
Tabata Y, Ikada Y (1987) Macrophage activation through phagocytosis of muramyl dipeptide encapsulated in gelatin microspheres. J Pharm Pharmacol 39(9):698–704
Evans JT et al (2003) Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert Rev Vaccines 2(2):219–229
Baldridge JR, Crane RT (1999) Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines. Methods 19(1):103–107
Mata-Haro V et al (2007) The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 316(5831):1628–1632
Fries LF et al (1992) Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy. Proc Natl Acad Sci U S A 89(1):358–362
Zhou F, Huang L (1993) Monophosphoryl lipid A enhances specific CTL induction by a soluble protein antigen entrapped in liposomes. Vaccine 11(11):1139–1144
Chong CS et al (2005) Enhancement of T helper type 1 immune responses against hepatitis B virus core antigen by PLGA nanoparticle vaccine delivery. J Control Release 102(1):85–99
Thoelen S, De Clercq N, Tornieporth N (2001) A prophylactic hepatitis B vaccine with a novel adjuvant system. Vaccine 19(17–19):2400–2403
Thoelen S et al (1998) Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system. Vaccine 16(7):708–714
Moore A, McCarthy L, Mills KH (1999) The adjuvant combination monophosphoryl lipid A and QS21 switches T cell responses induced with a soluble recombinant HIV protein from Th2 to Th1. Vaccine 17(20–21):2517–2527
Reed SG et al (2003) Prospects for a better vaccine against tuberculosis. Tuberculosis (Edinb) 83(1–3):213–219
Krieg AM (2006) Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 5(6):471–484
Kwissa M, Kasturi SP, Pulendran B (2007) The science of adjuvants. Expert Rev Vaccines 6(5):673–684
Krishnamachari Y, Salem AK (2009) Innovative strategies for co-delivering antigens and CpG oligonucleotides. Adv Drug Deliv Rev 61(3):205–217
Roman M et al (1997) Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat Med 3(8):849–854
Oumouna M et al (2005) Formulation with CpG oligodeoxynucleotides prevents induction of pulmonary immunopathology following priming with formalin-inactivated or commercial killed bovine respiratory syncytial virus vaccine. J Virol 79(4):2024–2032
Oussoren C, Storm G (2001) Liposomes to target the lymphatics by subcutaneous administration. Adv Drug Deliv Rev 50(1–2):143–156
Malyala P et al (2008) The potency of the adjuvant, CpG oligos, is enhanced by encapsulation in PLG microparticles. J Pharm Sci 97(3):1155–1164
Zhang XQ et al (2007) Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. J Immunother 30(5):469–478
Intra J et al (2008) Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with hydrolytically degradable seals. J Control Release 127(3):280–287
Singh M et al (2006) Polylactide-co-glycolide microparticles with surface adsorbed antigens as vaccine delivery systems. Curr Drug Deliv 3:115–120
Judge AD et al (2005) Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 23(4):457–462
Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8(2):129–138
Alexopoulou L et al (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732–738
Kariko K et al (2004) Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J Immunol 172(11):6545–6549
Liu G et al (2004) Small interference RNA modulation of IL-10 in human monocyte-derived dendritic cells enhances the Th1 response. Eur J Immunol 34(6):1680–1687
Hill JA et al (2003) Immune modulation by silencing IL-12 production in dendritic cells using small interfering RNA. J Immunol 171(2):691–696
Jain S, Yap WT, Irvine DJ (2005) Synthesis of protein-loaded hydrogel particles in an aqueous two-phase system for coincident antigen and CpG oligonucleotide delivery to antigen-presenting cells. Biomacromolecules 6(5):2590–2600
Ali OA et al (2009) Infection-mimicking materials to program dendritic cells in situ. Nat Mater 8(2):151–158
Roy K et al (2003) Gene delivery with in-situ crosslinking polymer networks generates long-term systemic protein expression. Mol Ther 7(3):401–408
Hori Y et al (2008) Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy. Biomaterials 29(27):3671–3682
Hori Y, Winans AM, Irvine DJ (2009) Modular injectable matrices based on alginate solution/microsphere mixtures that gel in situ and co-deliver immunomodulatory factors. Acta Biomater 5(4):969–982
Singh A, Suri S, Roy K (2009) In-situ crosslinking hydrogels for combinatorial delivery of chemokines and siRNA-DNA carrying microparticles to dendritic cells. Biomaterials 30(28):5187–5200.10.1016/j.biomaterials.2009.06.001
Nochi T et al (2010) Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. Nat Mater 9(7):572–578
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Singh, A., Pradhan, P., Roy, K. (2013). Immunobioengineering Approaches Towards Combinatorial Delivery of Immune-Modulators and Antigens. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_8
Download citation
DOI: https://doi.org/10.1007/978-1-4614-5380-2_8
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-5379-6
Online ISBN: 978-1-4614-5380-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)