title: Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines.
abstract: In recent years microspheres or microparticles produced from biodegradable polymers such as poly(D,L-lactide) (PLA) and poly(D, L-lactide-co-glycolide) (PLGA) containing encapsulated vaccine antigens have been investigated for administration via parenteral, oral, and intranasal routes. These microparticles allow the controlled release of vaccines with an aim to reduce the number of doses for primary immunisation or to develop single dose vaccines. The polymer materials have been widely regarded as being of minimal toxicity. Evaluation of candidate systems in animal studies have shown antibody levels and cell responses similar to or greater than those observed with adjuvants such as alum. However, there are concerns regarding the integrity and immunogenicity of the antigen during the encapsulation process when the antigen is exposed to organic solvents, high shear stresses and the exposure of antigen to low pH which is caused by polymer degradation. An alternative approach would be to adsorb antigens to the surface of biodegradable polymer particles. Polymeric lamellar substrate particles (PLSP), produced by a simple precipitation of PLA, are suitable for this purpose. The adsorption of antigens onto these particles is a simple procedure. It avoids pH changes due to bulk polymer degradation and the use of solvents and therefore will be less damaging to the vaccine. Moreover, such systems will be much easier to scale up for a clinical study and eventual manufacture. The aim of this article is to discuss the preparation and physical characteristics of PLSP, antigen adsorption, in vivo efficacy of PLSP antigen systems and to consider the potential of PLSP as controlled release adjuvants for protein, peptide or viral vaccines.
authors.affiliation: Danbiosyst UK Ltd, Albert Einstein Centre, Highfields Science Park, Nottingham, UK.
authors.forename: I
authors.initials: I
authors.lastname: Jabbal-Gill
authors.forename: W
authors.initials: W
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: Jenkins
authors.forename: P
authors.initials: P
authors.lastname: Watts
authors.forename: M
authors.initials: M
authors.lastname: Jimenez
authors.forename: L
authors.initials: L
authors.lastname: Illum
authors.forename: S S
authors.initials: SS
authors.lastname: Davis
authors.forename: J M
authors.initials: JM
authors.lastname: Wood
authors.forename: D
authors.initials: D
authors.lastname: Major
authors.forename: P D
authors.initials: PD
authors.lastname: Minor
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: E C
authors.initials: EC
authors.lastname: Lavelle
authors.forename: A G
authors.initials: AG
authors.lastname: Coombes
mesh_terms: D000276:Adjuvants, Immunologic; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D011232:Chemical Precipitation; D051379:Mice; D010316:Particle Size; D010455:Peptides / Q000276:immunology; D011091:Polyesters; D014612:Vaccines / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001672:Biocompatible Materials; D010455:Peptides; D011091:Polyesters; D014612:Vaccines; D014765:Viral Vaccines; C033616:poly(lactide)