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. 1996 May;88(1):162–168. doi: 10.1046/j.1365-2567.1996.d01-639.x

Novel polymer-grafted starch microparticles for mucosal delivery of vaccines.

P L Heritage 1, L M Loomes 1, J Jianxiong 1, M A Brook 1, B J Underdown 1, M R McDermott 1
PMCID: PMC1456457  PMID: 8707344

Abstract

Recent studies have demonstrated that systemic and mucosal administration of soluble antigens in biodegradable microparticles can potentiate antigen-specific humoral and cellular immune responses. However, current microparticle formulations are not adequate for all vaccine antigens, necessitating the further development of microparticle carrier systems. In this study, we developed a novel microparticle fabrication technique in which human serum albumin (HSA) was entrapped in starch microparticles grafted with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS), a biocompatible silicone polymer. The immunogenicity of HSA was preserved during the microparticle fabrication process. Following intraperitoneal immunization of mice, TS-PDMS-grafted microparticles (MP) dramatically enhanced serum IgG responses compared with ungrafted MP and soluble HSA alone (P < 0.001). When delivered orally, both TS-PDMS-grafted and ungrafted microparticles elicited HSA-specific IgA responses in gut secretions, in contrast to orally administered soluble antigen. Indeed, TS-PDMS-grafted microparticles stimulated significantly stronger serum IgG (P < 0.005) and IgA (P < 0.001) responses compared with those elicited by ungrafted microparticles. These findings indicate that TS-PDMS-grafted starch microparticles have potential as systemic and mucosal vaccine delivery vehicles.

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Selected References

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  1. Alonso M. J., Gupta R. K., Min C., Siber G. R., Langer R. Biodegradable microspheres as controlled-release tetanus toxoid delivery systems. Vaccine. 1994 Mar;12(4):299–306. doi: 10.1016/0264-410x(94)90092-2. [DOI] [PubMed] [Google Scholar]
  2. Artursson P., Edman P., Laakso T., Sjöholm I. Characterization of polyacryl starch microparticles as carriers for proteins and drugs. J Pharm Sci. 1984 Nov;73(11):1507–1513. doi: 10.1002/jps.2600731103. [DOI] [PubMed] [Google Scholar]
  3. Challacombe S. J., Rahman D., Jeffery H., Davis S. S., O'Hagan D. T. Enhanced secretory IgA and systemic IgG antibody responses after oral immunization with biodegradable microparticles containing antigen. Immunology. 1992 May;76(1):164–168. [PMC free article] [PubMed] [Google Scholar]
  4. Cowsar D. R., Tice T. R., Gilley R. M., English J. P. Poly(lactide-co-glycolide) microcapsules for controlled release of steroids. Methods Enzymol. 1985;112:101–116. doi: 10.1016/s0076-6879(85)12010-0. [DOI] [PubMed] [Google Scholar]
  5. Dudding B. A., Top F. H., Jr, Scott R. M., Russell P. K., Buescher E. L. An analysis of hospitalizations for acute respiratory disease in recruits immunized with adenovirus type 4 and type 7 vaccines. Am J Epidemiol. 1972 Feb;95(2):140–147. doi: 10.1093/oxfordjournals.aje.a121378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eldridge J. H., Gilley R. M., Staas J. K., Moldoveanu Z., Meulbroek J. A., Tice T. R. Biodegradable microspheres: vaccine delivery system for oral immunization. Curr Top Microbiol Immunol. 1989;146:59–66. doi: 10.1007/978-3-642-74529-4_6. [DOI] [PubMed] [Google Scholar]
  7. Eldridge J. H., Staas J. K., Meulbroek J. A., Tice T. R., Gilley R. M. Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies. Infect Immun. 1991 Sep;59(9):2978–2986. doi: 10.1128/iai.59.9.2978-2986.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FAZEKAS DE ST GROTH S. Studies in experimental immunology of influenza. IX. The mode of action of pathotopic adjuvants. Aust J Exp Biol Med Sci. 1951 Sep;29(5):339–351. doi: 10.1038/icb.1951.40. [DOI] [PubMed] [Google Scholar]
  9. Guzman C. A., Molinari G., Fountain M. W., Rohde M., Timmis K. N., Walker M. J. Antibody responses in the serum and respiratory tract of mice following oral vaccination with liposomes coated with filamentous hemagglutinin and pertussis toxoid. Infect Immun. 1993 Feb;61(2):573–579. doi: 10.1128/iai.61.2.573-579.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jackson S., Mestecky J., Childers N. K., Michalek S. M. Liposomes containing anti-idiotypic antibodies: an oral vaccine to induce protective secretory immune responses specific for pathogens of mucosal surfaces. Infect Immun. 1990 Jun;58(6):1932–1936. doi: 10.1128/iai.58.6.1932-1936.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jani P., Halbert G. W., Langridge J., Florence A. T. The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. J Pharm Pharmacol. 1989 Dec;41(12):809–812. doi: 10.1111/j.2042-7158.1989.tb06377.x. [DOI] [PubMed] [Google Scholar]
  12. Joel D. D., Laissue J. A., LeFevre M. E. Distribution and fate of ingested carbon particles in mice. J Reticuloendothel Soc. 1978 Nov;24(5):477–487. [PubMed] [Google Scholar]
  13. Kenrick K. G., Cooper G. N. Antibodies in the intestinal secretions of rats. Primary and secondary responses to polymeric flagellin. Aust J Exp Biol Med Sci. 1978 Aug;56(4):441–452. doi: 10.1038/icb.1978.50. [DOI] [PubMed] [Google Scholar]
  14. Laccourreye O., Laurent A., Polivka M., Wassef M., Domas L., Brasnu D., Merland J. J. Biodegradable starch microspheres for cerebral arterial embolization. Invest Radiol. 1993 Feb;28(2):150–154. doi: 10.1097/00004424-199302000-00014. [DOI] [PubMed] [Google Scholar]
  15. Lefevre M. E., Joel D. D., Schidlovsky G. Retention of ingested latex particles in Peyer's patches of germfree and conventional mice. Proc Soc Exp Biol Med. 1985 Sep;179(4):522–528. doi: 10.3181/00379727-179-42133. [DOI] [PubMed] [Google Scholar]
  16. Markwell M. A., Fox C. F. Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril. Biochemistry. 1978 Oct 31;17(22):4807–4817. doi: 10.1021/bi00615a031. [DOI] [PubMed] [Google Scholar]
  17. Marx P. A., Compans R. W., Gettie A., Staas J. K., Gilley R. M., Mulligan M. J., Yamshchikov G. V., Chen D., Eldridge J. H. Protection against vaginal SIV transmission with microencapsulated vaccine. Science. 1993 May 28;260(5112):1323–1327. doi: 10.1126/science.8493576. [DOI] [PubMed] [Google Scholar]
  18. McDermott M. R., Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979 May;122(5):1892–1898. [PubMed] [Google Scholar]
  19. McDermott M. R., Smiley J. R., Leslie P., Brais J., Rudzroga H. E., Bienenstock J. Immunity in the female genital tract after intravaginal vaccination of mice with an attenuated strain of herpes simplex virus type 2. J Virol. 1984 Sep;51(3):747–753. doi: 10.1128/jvi.51.3.747-753.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Melnick J. L. Advantages and disadvantages of killed and live poliomyelitis vaccines. Bull World Health Organ. 1978;56(1):21–38. [PMC free article] [PubMed] [Google Scholar]
  21. Michalek S. M., Childers N. K., Katz J., Denys F. R., Berry A. K., Eldridge J. H., McGhee J. R., Curtiss R., 3rd Liposomes as oral adjuvants. Curr Top Microbiol Immunol. 1989;146:51–58. doi: 10.1007/978-3-642-74529-4_5. [DOI] [PubMed] [Google Scholar]
  22. Moldoveanu Z., Novak M., Huang W. Q., Gilley R. M., Staas J. K., Schafer D., Compans R. W., Mestecky J. Oral immunization with influenza virus in biodegradable microspheres. J Infect Dis. 1993 Jan;167(1):84–90. doi: 10.1093/infdis/167.1.84. [DOI] [PubMed] [Google Scholar]
  23. Mowat A. M., Donachie A. M., Reid G., Jarrett O. Immune-stimulating complexes containing Quil A and protein antigen prime class I MHC-restricted T lymphocytes in vivo and are immunogenic by the oral route. Immunology. 1991 Mar;72(3):317–322. [PMC free article] [PubMed] [Google Scholar]
  24. Mowat A. M., Maloy K. J., Donachie A. M. Immune-stimulating complexes as adjuvants for inducing local and systemic immunity after oral immunization with protein antigens. Immunology. 1993 Dec;80(4):527–534. [PMC free article] [PubMed] [Google Scholar]
  25. O'Hagan D. T., Jeffery H., Roberts M. J., McGee J. P., Davis S. S. Controlled release microparticles for vaccine development. Vaccine. 1991 Oct;9(10):768–771. doi: 10.1016/0264-410x(91)90295-h. [DOI] [PubMed] [Google Scholar]
  26. O'Hagan D. T., McGee J. P., Holmgren J., Mowat A. M., Donachie A. M., Mills K. H., Gaisford W., Rahman D., Challacombe S. J. Biodegradable microparticles for oral immunization. Vaccine. 1993;11(2):149–154. doi: 10.1016/0264-410x(93)90011-l. [DOI] [PubMed] [Google Scholar]
  27. Pappo J., Ermak T. H. Uptake and translocation of fluorescent latex particles by rabbit Peyer's patch follicle epithelium: a quantitative model for M cell uptake. Clin Exp Immunol. 1989 Apr;76(1):144–148. [PMC free article] [PubMed] [Google Scholar]
  28. Santiago N., Milstein S., Rivera T., Garcia E., Zaidi T., Hong H., Bucher D. Oral immunization of rats with proteinoid microspheres encapsulating influenza virus antigens. Pharm Res. 1993 Aug;10(8):1243–1247. doi: 10.1023/a:1018992924025. [DOI] [PubMed] [Google Scholar]
  29. Weisz-Carrington P., Roux M. E., McWilliams M., PHILLIPS-Quagliata J. M., Lamm M. E. Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system. J Immunol. 1979 Oct;123(4):1705–1708. [PubMed] [Google Scholar]

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