FIELD OF THE INVENTION The invention relates to the fields of antigen delivery and vaccines. More specifically, the invention relates to certain microparticles, and to antigen delivery and vaccine immunization strategies employing such microparticles. The invention in particular relates to microparticles that are useful in the prophylaxis and treatment of human immunodeficiency virus (HIV) infections. BACKGROUND OF THE INVENTION It is important that therapeutic or prophylactic peptides, and in particular vaccines, are efficiently delivered to their site of action without significant degradation. Polymeric microparticles encapsulating peptide antigens have been investigated as potential delivery systems for their capability to efficiently target the antigen to professional antigen-presenting cells and to release it in a controlled way over a prolonged period of time (O'Hagan D T., Recent advances in vaccine adjuvants for systemic and mucosal administration, J. Pharm. Pharmacol., 1998; 59:1-10; Nugent J, Wan Po L, Scott E., Design and delivery of non-parental vaccines, Review. J. Clin. Pharm. Therap., 1998; 23:257-85; and Alpar H O, Ward K R, Williamson E D., New strategies in vaccine delivery., S.T.P. Pharma Sci., 2000; 10:269-78). Although peptides encapsulated into a microparticulate matrix may be protected from unfavorable conditions encountered after parenteral or mucosal administration (Nedrud J G, Lamm M E., Adjuvants and the mucosal immune system, In: Spriggs D R, Koff W C, editors, Topics in vaccine adjuvant research, Boca Raton: CRC, 1991. p. 51 -67), they often become unstable or are degraded. This may occur either during the encapsulation process, such as the exposure to organic solvents, high shear and freeze-drying, and/or in the body when the antigen is exposed to the low pH microenvironment caused by the degradation of the polymer (O'Hagan D T, Singh M, Gupta R K., Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines, Adv. Drug. Deliv. Rev. 1998; 32:22546; and O'Hagan D T., supra). SUMMARY OF THE INVENTION The inventors have found that antigens may be fixed or adsorbed to the external surface of polymeric microparticles. Further the inventors have shown that these microparticles may be used to efficiently deliver antigens to target cells. Accordingly the invention provides a microparticle comprising: (a) a core which comprises a water insoluble polymer or copolymer, and (b) a shell which comprises a hydrophilic polymer or copolymer and functional groups which are ionic or ionisable; said microparticle having a disease-associated antigen adsorbed at the external surface. The invention further provides: - a method of production of a microparticle of invention; - a pharmaceutical composition comprising a microparticle of the invention; - a method of generating an immune response in an individual, said method comprising administering a microparticle of the invention in a therapeutically effective amount; - a method of preventing or treating HIV infection or AIDS, said method comprising administering a microparticle of the invention in a therapeutically effective amount. - a microparticle of the invention for use in a method of treatment of the human or animal body by therapy or diagnosis; - use of a microparticle of the invention for the manufacture of a medicament for generating an immune response in an individual; and - use of a microparticle of the invention for the manufacture of a medicament for preventing or treating HIV infection or AIDS.

Use of microparticles for antigen delivery

CAPUTO A;GAVIOLI, Riccardo;
2003

Abstract

FIELD OF THE INVENTION The invention relates to the fields of antigen delivery and vaccines. More specifically, the invention relates to certain microparticles, and to antigen delivery and vaccine immunization strategies employing such microparticles. The invention in particular relates to microparticles that are useful in the prophylaxis and treatment of human immunodeficiency virus (HIV) infections. BACKGROUND OF THE INVENTION It is important that therapeutic or prophylactic peptides, and in particular vaccines, are efficiently delivered to their site of action without significant degradation. Polymeric microparticles encapsulating peptide antigens have been investigated as potential delivery systems for their capability to efficiently target the antigen to professional antigen-presenting cells and to release it in a controlled way over a prolonged period of time (O'Hagan D T., Recent advances in vaccine adjuvants for systemic and mucosal administration, J. Pharm. Pharmacol., 1998; 59:1-10; Nugent J, Wan Po L, Scott E., Design and delivery of non-parental vaccines, Review. J. Clin. Pharm. Therap., 1998; 23:257-85; and Alpar H O, Ward K R, Williamson E D., New strategies in vaccine delivery., S.T.P. Pharma Sci., 2000; 10:269-78). Although peptides encapsulated into a microparticulate matrix may be protected from unfavorable conditions encountered after parenteral or mucosal administration (Nedrud J G, Lamm M E., Adjuvants and the mucosal immune system, In: Spriggs D R, Koff W C, editors, Topics in vaccine adjuvant research, Boca Raton: CRC, 1991. p. 51 -67), they often become unstable or are degraded. This may occur either during the encapsulation process, such as the exposure to organic solvents, high shear and freeze-drying, and/or in the body when the antigen is exposed to the low pH microenvironment caused by the degradation of the polymer (O'Hagan D T, Singh M, Gupta R K., Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines, Adv. Drug. Deliv. Rev. 1998; 32:22546; and O'Hagan D T., supra). SUMMARY OF THE INVENTION The inventors have found that antigens may be fixed or adsorbed to the external surface of polymeric microparticles. Further the inventors have shown that these microparticles may be used to efficiently deliver antigens to target cells. Accordingly the invention provides a microparticle comprising: (a) a core which comprises a water insoluble polymer or copolymer, and (b) a shell which comprises a hydrophilic polymer or copolymer and functional groups which are ionic or ionisable; said microparticle having a disease-associated antigen adsorbed at the external surface. The invention further provides: - a method of production of a microparticle of invention; - a pharmaceutical composition comprising a microparticle of the invention; - a method of generating an immune response in an individual, said method comprising administering a microparticle of the invention in a therapeutically effective amount; - a method of preventing or treating HIV infection or AIDS, said method comprising administering a microparticle of the invention in a therapeutically effective amount. - a microparticle of the invention for use in a method of treatment of the human or animal body by therapy or diagnosis; - use of a microparticle of the invention for the manufacture of a medicament for generating an immune response in an individual; and - use of a microparticle of the invention for the manufacture of a medicament for preventing or treating HIV infection or AIDS.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/498428
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