Micro- and Nanoparticle-Based Vaccines for Hepatitis B

  • Dhruba J. Bharali
  • Shaker A. Mousa
  • Yasmin Thanavala
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


The incredible success of vaccinations in contributing to public health is undeniable.In fact, vaccines are the most cost-effective public health tool for disease preventionbecause their cost is less than the combined costs of treatment, hospitalization, and time lossfrom work. However, despite the availability of vaccines, cost per dose is a factor limiting thesuccess of global vaccination campaigns, as are the limitations imposed by the need of deliveringmultiple vaccine doses. A number of approaches are being tested particularly for the deliveryof subunit vaccines, and in recent years, a number of groups have devoted their efforts todevelop nano/microparticles prepared from biodegradable and biocompatible polymers asvaccine delivery systems with the goal of inducing both humoral and cellular immune responses.Some important properties of biodegradable polymers are their documented safetyhistory, biocompatibility, and an ability to provide controlled time/rate of antigen release andpolymer degradation. The most extensively studied polymer used for encapsulating vaccineantigens is poly (lactide-co-glycolide acid) (PLGA). This chapter deals in brief with effortstargeting the use of PLGA micro-and nanoparticles for the delivery of hepatitis B surfaceantigen.


PLGA Microsphere Tree Shrew PLGA Nanoparticles Oral Immunization PLGA Microparticle 
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  1. Cleland, J.L., Lim, A., Barron, L., Duenas, E.T. and Powell, M.F. (1997) Development of a single-shot subunit vaccine for HIV-1: Part 4. Optimizing microencapsulation and pulsatile release of MN rgp120 from biodegradable microspheres. J. Control Release 47, 135–150.CrossRefGoogle Scholar
  2. Clements, C.J. and Griffiths, E. (2002) The global impact of vaccines containing aluminium adjuvants. Vaccine 20, S24–S33.CrossRefPubMedGoogle Scholar
  3. Davis, J.P. (2005) Experience with hepatitis A and B vaccines. Am. J. Med. 118, 7S–15S.CrossRefPubMedGoogle Scholar
  4. Davis, H.L., McCluskie, M.J., Gerin, J.L. and Purcell, R.H. (1996) DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. USA 93, 7213–7218.CrossRefPubMedGoogle Scholar
  5. Duncan, J.D., Gilley, R.M., Schafer, D.P., Moldoveanu Z. and Mestecky J.F. (1996) Poly(lactide-co-glycolide) microencapsulation of vaccines for mucosal immunization. In: H. Kiyono, P.L. Ogra and J.R. McGhee (Eds.), Mucosal Vaccines, Academic Press, San Diego, pp. 159–174.CrossRefGoogle Scholar
  6. Eldridge, J., Gilley, R., Staas, R., Moldoveanu, Z., Muelbroek, J. and Tice T. (1989) Biodegradable microspheres: vaccine delivery system for oral immunization. Curr. Top. Microbiol. Immunol. 146, 59–66.PubMedGoogle Scholar
  7. Eldridge, J.H., Staas, J.K., Tice, T.R. and Gilley, R.M. (1992) Biodegradable poly(lactide-co-glycolide) microspheres. Res. Immunol. 143, 557–563.CrossRefPubMedGoogle Scholar
  8. Fong, F.W. (1979) Microsphere production from particle dispersion in polymer solution by adding phase separation agent at low temperature. US Patent US 4, 166, 800.Google Scholar
  9. Gabor, F., Scwarzbauer, A. and Wirth, M. (2002) Lectin mediated drug delivery: binding and uptake of BSA-WGA conjugates using the caco-2 model. Int. J. Pharm. 237, 227–239.CrossRefPubMedGoogle Scholar
  10. Gupta, R.K., Chang, A.C., Griffin, P., Rivera, R., Guo, Y.Y. and Siber G.R. (1997) Determination of protein loading in biodegradable polymer microspheres containing tetanus toxoid. Vaccine 15, 672–678.CrossRefPubMedGoogle Scholar
  11. Gupta, P.N., Mahor S., Rawat, A., Khatri, K., Goyal, A. and Vyas, S.P. (2006) Lectin anchored stabilized biodegradable nanoparticles for oral immunization 1. Development and in vitro evaluation. Int. J.Pharm. 318, 163–173.CrossRefPubMedGoogle Scholar
  12. Gupta, R.K. and Siber G.R. (1995) Adjuvants for human vaccines-current status, problems and future prospects. Vaccine 13, 1263–1276.CrossRefPubMedGoogle Scholar
  13. He, X., Wang, F., Jiang, L., Li, J., Liu, S., Xiao, Z., Jin, X., Zhang, Y., He, Y., Li, K., Guo, Y. and Sun, S. (2005) Induction of mucosal and systemic immune response by single-dose oral immunization with biodegradable microparticles containing DNA encoding HBsAg. J. Gen. Virol. 86, 601–661.CrossRefPubMedGoogle Scholar
  14. Jaganathan, K.S. and Vyas, S.P. (2006) Strong systemic and mucosal immune responses to surface-modifies PLGA microspheres containing recombinant Hepatitis B antigen administered intranasally. Vaccine 24, 4201–4211.CrossRefPubMedGoogle Scholar
  15. Jain, S., Singh, P., Mishra, V. and Vyas, S.P. (2005) Mannosylated niosomes as adjuvant–carrier system for oral genetic immunization against Hepatitis B. Immunol. Lett. 101, 41–49.CrossRefPubMedGoogle Scholar
  16. Jiang, W., Gupta, R.K., Deshpande, M.C. and Schwendeman, S.P. (2005) Biodegradable poly(lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv. Drug Del. Rev. 57, 391–410.CrossRefGoogle Scholar
  17. Kavanagh, O.V., Early, B., Murray, M., Foster, C.J. and Adair, B.M. (2003)Antigenspecific IgA and IgG responses in calves inoculated intranasally with ovalbumin encapsulated in poly(dl-lactide-co-glycolide) microspheres. Vaccine 21, 4472–4480.CrossRefPubMedGoogle Scholar
  18. Kersten, G. and Hirshberg, H. (2004) Antigen delivery systems. Expert Rev.Vaccines 3, 453–462.CrossRefPubMedGoogle Scholar
  19. Kersten, G.F.A. and Kaufmann, G.B. (1996) Biodegradable microspheres as vehicles for antigens. In: W. deGruyter (Eds.) Concepts in Vaccine Development. New York, Springer Publ. Co., pp. 265–302.Google Scholar
  20. Lavelle, E.C., Grant, G., Pfuller, U. and O’Hagan, D.T. (2004) Immunological implication of the use of plant lectins for drug and vaccine targeting to the gastrointestinal tract. J. Drug Target. 12, 89–95.CrossRefPubMedGoogle Scholar
  21. Lavelle, E.C., Grant, G., Pusztai, A., Fuller, U. and O’Hagan, D.T. (2001)Identification of plant lectin with mucosal adjuvant activity. Immunology 102, 77–86.Google Scholar
  22. Le Guerhier, F., Thermet, A., Guerret, S., Chevallier, M., Jamard, C., Gibbs, C.S., Trepo, C., Cova, L. and Zoulim, F. (2003) Antiviral effect of adefovir in combination with a DNA vaccine in the duck hepatitis B virus infection model. J. Hepatol. 38, 328–334.CrossRefPubMedGoogle Scholar
  23. McNeela, E., O’Connor, D., Jabbal-Gill, I., Illum, L., Davis, S.S., Pizza, M., Peppoloni, S., Rappuoli, R. and Mills, K.H.G. (2000) A mucosally delivered vaccine against diphtheria: formulation of cross reacting material (CRM197) of diphtheria toxin with chitosan enhances local and systemic and Th2 responses following nasal delivery. Vaccine 19, 1188–1198.CrossRefPubMedGoogle Scholar
  24. McGee, J.P., Singh, M., Li, X.M., Qui, H. and O’Hagan, D.T. (1997) The encapsulation of a model protein in poly (lactide-co-glycolide) microparticles of various sizes; an evaluation of process reproducibility, J. Microencapsul. 14, 197–210.CrossRefPubMedGoogle Scholar
  25. Nuwayser, E.S. and Nucefora, W.A. (1986) Controlled release mi-croparticles comprising core of active ingredient and polymer and coating of the same polymer. US Patent US4, 623, 588.Google Scholar
  26. O’Hagan, D.T., Jeffery H. and Davis S.S. (1993) The preparation and characterization of poly (lactide-co-glycolide) microparticles II. The entrapment of a model protein using a water-in-oil-inwater emulsion solvent evaporation technique. Pharm. Res. 10, 362–368.CrossRefPubMedGoogle Scholar
  27. Oka, Y., Akbar, S.M., Horiike, N., Joko, K. and Onji, M. (2001) Mechanism and therapeutic potential of DNA-based immunization against the envelope proteins of hepatitis B virus in normal and transgenic mice. Immunology 103, 90–97.Google Scholar
  28. Park, K., Shalaby, W.S.W. and Park H. (1993) Biodegradable Hydrogels for Drug Delivery. Technomic Publishing Company, Inc., Pennsylvania.Google Scholar
  29. Rajkannan, R., Dhanaraju, M.D., Gopinath, D., Selvaraj, D. and Jayakumar, R. (2006) Development of hepatitis B oral vaccine using B cell epitope loaded PLG microparticles. Vaccine 24, 5149–5157.CrossRefPubMedGoogle Scholar
  30. Shalaby, W.S.W. (1995) Development of oral vaccines to stimulate mucosal andsystemic immunity: barriers and novel strategies. Clin. Immunol. Immunopathol. 74, 127–134.CrossRefPubMedGoogle Scholar
  31. Singh, P., Prabhakaran, D., Jain, S., Mishra, V., Jaganathan, K.S. and Vyas, S.P. (2004) Cholera toxin B conjugated bile salt stabilized vesicles (bilosomes) for oral immunization Int. J. Pharm. 278, 379–390.Google Scholar
  32. Spiers, I.D., Eyles, J.E., Baillie, L.W.J., Williamson, E.D. and Oya Alpar, H. (2000) Biodegradable microparticles with different release profiles: effect on the immune response after a single administration via intranasal and intramuscular routes. J. Pharm. Pharmacol. 52, 1195–1201.CrossRefPubMedGoogle Scholar
  33. Tambera, H., Johansena, P., Merklea, H.P. and Gander, B. (2005) Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv. Drug Del. Rev. 57, 357– 376.CrossRefGoogle Scholar
  34. Thoelen, S., Clercq, N.D. and Tornieporth, N.A. (2001) Prophylactic hepatitis B vaccine with a novel adjuvant system. Vaccine 19, 2400–2403.CrossRefPubMedGoogle Scholar
  35. Vady, M. and O’Hagan, D.T. (1996) Microparticles for intranasal immunization, Adv. Drug Del. Rev. 21, 33–47.CrossRefGoogle Scholar
  36. Van der, L.I.M., Kersten, G., Fretz, M.M., Beuvery, C., Verhoef, J.C. and Junginger, H.E. (2003) Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine 21, 1400–1408.CrossRefGoogle Scholar
  37. Wikingsson, L. and Sjoholm, I. (2002) Polyacryl starch microparticles as adjuvant in oral immunization, inducing mucosal and systemic immune responses in mice. Vaccine 20, 3353–3363.CrossRefGoogle Scholar
  38. Zhou, F.J., Hu, Z.L., Dai, J.X., Chen, R.W., Shi, K., Lin, Y. and Sun, S.H. (2003) Protection of tree shrews by pVAX-PS DNA vaccine against HBV infection. DNA Cell Biol. 22, 475–478.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Dhruba J. Bharali
    • 1
  • Shaker A. Mousa
    • 2
  • Yasmin Thanavala
    • 1
  1. 1.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Pharmaceutical Research Institute at Albany, Albany College of PharmacyAlbanyUSA

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