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

L Donnelly, Rhonda M Curran, RJ Morrow, VL Kett, GP Andrews, RK Malcolm, AD Woolfson, RJ Shattock

    Research output: Contribution to journalArticle

    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.
    LanguageEnglish
    Pages156
    JournalRetrovirology
    Volume6 (sup
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    Intravaginal Administration
    HIV-1
    Vaccines
    Gels
    Antigens
    Immunoglobulin G
    Refrigeration
    Carboxymethylcellulose Sodium
    Freeze Drying
    Immunoglobulin A
    Tablets
    Immunization
    Proteins
    Enzyme-Linked Immunosorbent Assay
    HIV
    Rabbits

    Cite this

    Donnelly, L., Curran, R. M., Morrow, RJ., Kett, VL., Andrews, GP., Malcolm, RK., ... Shattock, RJ. (2009). Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140. Retrovirology, 6 (sup, 156. https://doi.org/10.1186/1742-4690-6-S3-P156
    Donnelly, L ; Curran, Rhonda M ; Morrow, RJ ; Kett, VL ; Andrews, GP ; Malcolm, RK ; Woolfson, AD ; Shattock, RJ. / Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140. In: Retrovirology. 2009 ; Vol. 6 (sup. pp. 156.
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    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.",
    author = "L Donnelly and Curran, {Rhonda M} and RJ Morrow and VL Kett and GP Andrews and RK Malcolm and AD Woolfson and RJ Shattock",
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    Donnelly, L, Curran, RM, Morrow, RJ, Kett, VL, Andrews, GP, Malcolm, RK, Woolfson, AD & Shattock, RJ 2009, 'Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140', Retrovirology, vol. 6 (sup, pp. 156. https://doi.org/10.1186/1742-4690-6-S3-P156

    Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140. / Donnelly, L; Curran, Rhonda M; Morrow, RJ; Kett, VL; Andrews, GP; Malcolm, RK; Woolfson, AD; Shattock, RJ.

    In: Retrovirology, Vol. 6 (sup, 2009, p. 156.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Stable lyophilised gel vehicles for vaginal administration ofrecombinant C-clade HIV-1 trimeric CN54gp140

    AU - Donnelly, L

    AU - Curran, Rhonda M

    AU - Morrow, RJ

    AU - Kett, VL

    AU - Andrews, GP

    AU - Malcolm, RK

    AU - Woolfson, AD

    AU - Shattock, RJ

    PY - 2009

    Y1 - 2009

    N2 - 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.

    AB - 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.

    U2 - 10.1186/1742-4690-6-S3-P156

    DO - 10.1186/1742-4690-6-S3-P156

    M3 - Article

    VL - 6 (sup

    SP - 156

    JO - Retrovirology

    T2 - Retrovirology

    JF - Retrovirology

    SN - 1742-4690

    ER -