TY - JOUR

T1 - Immunostimulatory lipid implants containing Quil-A and DC-cholesterol

AU - Myschik, Julia

AU - McBurney, Warren T

AU - Rades, Thomas

AU - Hook, Sarah

PY - 2008

Y1 - 2008

N2 - Biocompatible lipid implants which promote the sustained release of antigen have potential as novel vaccine delivery systems for subunit antigen as they may reduce or remove the requirement for multiple administrations. Of particular interest are sustained release systems that release antigen incorporated into particles. Previous work has demonstrated that lipid implants prepared from phosphatidylcholine, cholesterol, the adjuvant Quil-A, and ovalbumin as the model antigen could stimulate an immune response equivalent to that induced by a prime and boost with a comparable injectable vaccine. However, entrapment of antigen into particles released from the implant was low. Therefore the aim of this study was to firstly determine if the inclusion of a cationic derivative of cholesterol, DC-cholesterol, into the implants increased antigen entrapment and immunogenicity, and secondly, if a cationic implant could induce at least a comparable immune response as compared to a prime and boost with an injectable vaccine. The inclusion of DC-cholesterol had only a minor effect on antigen entrapment into particles released from the implants and the implants did not stimulate cellular responses as effectively as the comparable injectable vaccine or the unmodified implant containing Quil-A and cholesterol, although the vaccine did induce stronger responses than either soluble protein alone, or protein co-delivered in alum.

AB - Biocompatible lipid implants which promote the sustained release of antigen have potential as novel vaccine delivery systems for subunit antigen as they may reduce or remove the requirement for multiple administrations. Of particular interest are sustained release systems that release antigen incorporated into particles. Previous work has demonstrated that lipid implants prepared from phosphatidylcholine, cholesterol, the adjuvant Quil-A, and ovalbumin as the model antigen could stimulate an immune response equivalent to that induced by a prime and boost with a comparable injectable vaccine. However, entrapment of antigen into particles released from the implant was low. Therefore the aim of this study was to firstly determine if the inclusion of a cationic derivative of cholesterol, DC-cholesterol, into the implants increased antigen entrapment and immunogenicity, and secondly, if a cationic implant could induce at least a comparable immune response as compared to a prime and boost with an injectable vaccine. The inclusion of DC-cholesterol had only a minor effect on antigen entrapment into particles released from the implants and the implants did not stimulate cellular responses as effectively as the comparable injectable vaccine or the unmodified implant containing Quil-A and cholesterol, although the vaccine did induce stronger responses than either soluble protein alone, or protein co-delivered in alum.

U2 - 10.1016/j.ijpharm.2008.07.014

DO - 10.1016/j.ijpharm.2008.07.014

M3 - Journal article

C2 - 18692555

VL - 363

SP - 91

EP - 98

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -