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Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Donnelly, L, Curran, Rhonda M, Morrow, RJ, Kett, VL, Andrews, GP, Malcolm, RK, Woolfson, AD and Shattock, RJ (2009) Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140. Retrovirology, 6 (suppl 3) . p. 156. [Journal article]

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URL: http://www.retrovirology.com/content/pdf/1742-4690-6-S3-P156.pdf

DOI: 10.1186/1742-4690-6-S3-P156

Abstract

BackgroundWith an effective vaccine being sought for the prevention of HIV transmission, current focus is upon a mucosal vaccine strategy providing protection at the viral point of entry. The full potential of these vaccines can only be realised with the development of successful delivery systems which are also capable of providing an environment conducive to antigen stability. Previously, rheologically structured vehicles (RSVs) were formulated to include therecombinant C-clade HIV-1 envelope protein CN54gp140, and intra-vaginal immunisation in rabbits induced significant systemic IgG and specific IgG and IgA in genital tract secretions. However, CN54gp140 stability within these aqueous formulations remains a concern. Here we investigate the formulation of CN54gp140 within modified lyophilised RSV matrices as a means of providing enhanced protein stabilisation.MethodsRSV formulations were prepared comprising mucoadhesive (polycarbophil, sodium carboxymethylcellulose) and vaginal fluid absorbing (polyvinylpyrrolidine) components. Using rheological analyses in combination with dispensing studies, formulations having appropriate flow properties were chosen for lyophilisation. In vitro release testing of the lyophilised CN54gp140 formulations were investigated in PBST, and following prolonged storage at 37°C the antigenicity of CN54gp140 from the lyophilisedRSVs were analysed by ELISA. The antigen CN54gp140 stability profiles of these formulations were compared to the original aqueous RSV.ResultsCN54gp140 was found to be uniformly distributed within the lyophilised products and exhibited a sustained release profile over an 8 hour period during which the lyophilised 'tablet' underwent complete dissolution in thesurrounding media. While recovery of CN54gp140 from the aqueous RSV diminished over 9 days, lyophilisationshowed no loss in CN54gp140 antigenicity over 67 days storage.ConclusionFormulation of CN54gp140 within a lyophilised gel matrix is shown to have a stabilising effect on the antigen while preserving its sustained release capacity. Such a mucosal vaccine delivery system may offer numerous advantages including ease of use, long-term stability and cold chain avoidance.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Nursing
Research Institutes and Groups:Institute of Nursing and Health Research
Institute of Nursing and Health Research > Maternal, Fetal and Infant Research
ID Code:23200
Deposited By:Dr Rhonda Curran
Deposited On:31 Aug 2012 11:49
Last Modified:31 Aug 2012 11:49

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