A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140

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

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    BackgroundCervicovaginal (CV) tissue is the primary site for HIV transmission and a major reservoir for viral replication. Therefore, a successful vaccine strategy should induce potent immune responses at this mucosal surface. One potential method for achieving a localised immuneresponse is to administer the antigen directly to the CV tissue (Marx et al., 1993, Wassen et al., 1996). The aim of the study was to evaluate the in vitro release characteristics oflyophilised hydroxypropylmethylcellulose (HPMC) gel inserts containing HIV envelope protein CN54gp140 either as stand-alone formulations or located within a novel rod-insert vaginal ring device (RIVR).MethodsVaginal gel formulations comprising either low or high molecular weight (MW) HPMC and CN54gp140 (0.25% w/w) were prepared. The gels were injected into silicone elastomer tubing, cut to 40 mm lengths, and then lyophilised to produce solid rod inserts. In vitro release testing was performed on rod inserts alone and rod insert vaginal rings (RIVRs) containing two CN54gp140-loaded rod inserts. Release of gp140 was quantified by ELISA.ResultsRelease of CN54gp140 from rods prepared from low MW HPMC was similar for both inserts alone and rings containing inserts (99% cf. 90% over two hr). Release from the high MW inserts was significantly slower and more sustained than the low MW formulations. Also, CN54gp140 release from high MW rod inserts rings (68% of theoretical over 48 hr) was significantly more sustained than high MW inserts alone (86% over 24 hr).ConclusionThe study demonstrates that CN54gp140 (i) maintains its antigenicity during the preparation of HPMC lyophilised rod inserts, and (ii) may be administered in a sustainedmanner when the inserts are placed into an RIVR device. This stable, sustained-release formulation strategy has the potential to induce stronger immune responses andimmune memory upon vaginal administration (Zhao and Leong, 1996; Lofthouse, 2002).
    LanguageEnglish
    Pages157
    JournalRetrovirology
    Volume6 (sup
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    Female Contraceptive Devices
    HIV-1
    Molecular Weight
    Equipment and Supplies
    Gels
    Intravaginal Administration
    Human Immunodeficiency Virus Proteins
    Silicone Elastomers
    Mucosal Immunity
    Vaccines
    Enzyme-Linked Immunosorbent Assay
    HIV
    Antigens
    Hypromellose Derivatives

    Cite this

    Morrow, RJ., Donnelly, L., Curran, R. M., Malcolm, RK., Woolfson, AD., Andrews, GP., & Shattock, RJ. (2009). A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140. Retrovirology, 6 (sup, 157. https://doi.org/10.1186/1742-4690-6-S3-P157
    Morrow, RJ ; Donnelly, L ; Curran, Rhonda M ; Malcolm, RK ; Woolfson, AD ; Andrews, GP ; Shattock, RJ. / A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140. In: Retrovirology. 2009 ; Vol. 6 (sup. pp. 157.
    @article{622359dcc15746158e494e43b325f6ee,
    title = "A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140",
    abstract = "BackgroundCervicovaginal (CV) tissue is the primary site for HIV transmission and a major reservoir for viral replication. Therefore, a successful vaccine strategy should induce potent immune responses at this mucosal surface. One potential method for achieving a localised immuneresponse is to administer the antigen directly to the CV tissue (Marx et al., 1993, Wassen et al., 1996). The aim of the study was to evaluate the in vitro release characteristics oflyophilised hydroxypropylmethylcellulose (HPMC) gel inserts containing HIV envelope protein CN54gp140 either as stand-alone formulations or located within a novel rod-insert vaginal ring device (RIVR).MethodsVaginal gel formulations comprising either low or high molecular weight (MW) HPMC and CN54gp140 (0.25{\%} w/w) were prepared. The gels were injected into silicone elastomer tubing, cut to 40 mm lengths, and then lyophilised to produce solid rod inserts. In vitro release testing was performed on rod inserts alone and rod insert vaginal rings (RIVRs) containing two CN54gp140-loaded rod inserts. Release of gp140 was quantified by ELISA.ResultsRelease of CN54gp140 from rods prepared from low MW HPMC was similar for both inserts alone and rings containing inserts (99{\%} cf. 90{\%} over two hr). Release from the high MW inserts was significantly slower and more sustained than the low MW formulations. Also, CN54gp140 release from high MW rod inserts rings (68{\%} of theoretical over 48 hr) was significantly more sustained than high MW inserts alone (86{\%} over 24 hr).ConclusionThe study demonstrates that CN54gp140 (i) maintains its antigenicity during the preparation of HPMC lyophilised rod inserts, and (ii) may be administered in a sustainedmanner when the inserts are placed into an RIVR device. This stable, sustained-release formulation strategy has the potential to induce stronger immune responses andimmune memory upon vaginal administration (Zhao and Leong, 1996; Lofthouse, 2002).",
    author = "RJ Morrow and L Donnelly and Curran, {Rhonda M} and RK Malcolm and AD Woolfson and GP Andrews and RJ Shattock",
    year = "2009",
    doi = "10.1186/1742-4690-6-S3-P157",
    language = "English",
    volume = "6 (sup",
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    Morrow, RJ, Donnelly, L, Curran, RM, Malcolm, RK, Woolfson, AD, Andrews, GP & Shattock, RJ 2009, 'A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140', Retrovirology, vol. 6 (sup, pp. 157. https://doi.org/10.1186/1742-4690-6-S3-P157

    A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140. / Morrow, RJ; Donnelly, L; Curran, Rhonda M; Malcolm, RK; Woolfson, AD; Andrews, GP; Shattock, RJ.

    In: Retrovirology, Vol. 6 (sup, 2009, p. 157.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140

    AU - Morrow, RJ

    AU - Donnelly, L

    AU - Curran, Rhonda M

    AU - Malcolm, RK

    AU - Woolfson, AD

    AU - Andrews, GP

    AU - Shattock, RJ

    PY - 2009

    Y1 - 2009

    N2 - BackgroundCervicovaginal (CV) tissue is the primary site for HIV transmission and a major reservoir for viral replication. Therefore, a successful vaccine strategy should induce potent immune responses at this mucosal surface. One potential method for achieving a localised immuneresponse is to administer the antigen directly to the CV tissue (Marx et al., 1993, Wassen et al., 1996). The aim of the study was to evaluate the in vitro release characteristics oflyophilised hydroxypropylmethylcellulose (HPMC) gel inserts containing HIV envelope protein CN54gp140 either as stand-alone formulations or located within a novel rod-insert vaginal ring device (RIVR).MethodsVaginal gel formulations comprising either low or high molecular weight (MW) HPMC and CN54gp140 (0.25% w/w) were prepared. The gels were injected into silicone elastomer tubing, cut to 40 mm lengths, and then lyophilised to produce solid rod inserts. In vitro release testing was performed on rod inserts alone and rod insert vaginal rings (RIVRs) containing two CN54gp140-loaded rod inserts. Release of gp140 was quantified by ELISA.ResultsRelease of CN54gp140 from rods prepared from low MW HPMC was similar for both inserts alone and rings containing inserts (99% cf. 90% over two hr). Release from the high MW inserts was significantly slower and more sustained than the low MW formulations. Also, CN54gp140 release from high MW rod inserts rings (68% of theoretical over 48 hr) was significantly more sustained than high MW inserts alone (86% over 24 hr).ConclusionThe study demonstrates that CN54gp140 (i) maintains its antigenicity during the preparation of HPMC lyophilised rod inserts, and (ii) may be administered in a sustainedmanner when the inserts are placed into an RIVR device. This stable, sustained-release formulation strategy has the potential to induce stronger immune responses andimmune memory upon vaginal administration (Zhao and Leong, 1996; Lofthouse, 2002).

    AB - BackgroundCervicovaginal (CV) tissue is the primary site for HIV transmission and a major reservoir for viral replication. Therefore, a successful vaccine strategy should induce potent immune responses at this mucosal surface. One potential method for achieving a localised immuneresponse is to administer the antigen directly to the CV tissue (Marx et al., 1993, Wassen et al., 1996). The aim of the study was to evaluate the in vitro release characteristics oflyophilised hydroxypropylmethylcellulose (HPMC) gel inserts containing HIV envelope protein CN54gp140 either as stand-alone formulations or located within a novel rod-insert vaginal ring device (RIVR).MethodsVaginal gel formulations comprising either low or high molecular weight (MW) HPMC and CN54gp140 (0.25% w/w) were prepared. The gels were injected into silicone elastomer tubing, cut to 40 mm lengths, and then lyophilised to produce solid rod inserts. In vitro release testing was performed on rod inserts alone and rod insert vaginal rings (RIVRs) containing two CN54gp140-loaded rod inserts. Release of gp140 was quantified by ELISA.ResultsRelease of CN54gp140 from rods prepared from low MW HPMC was similar for both inserts alone and rings containing inserts (99% cf. 90% over two hr). Release from the high MW inserts was significantly slower and more sustained than the low MW formulations. Also, CN54gp140 release from high MW rod inserts rings (68% of theoretical over 48 hr) was significantly more sustained than high MW inserts alone (86% over 24 hr).ConclusionThe study demonstrates that CN54gp140 (i) maintains its antigenicity during the preparation of HPMC lyophilised rod inserts, and (ii) may be administered in a sustainedmanner when the inserts are placed into an RIVR device. This stable, sustained-release formulation strategy has the potential to induce stronger immune responses andimmune memory upon vaginal administration (Zhao and Leong, 1996; Lofthouse, 2002).

    U2 - 10.1186/1742-4690-6-S3-P157

    DO - 10.1186/1742-4690-6-S3-P157

    M3 - Article

    VL - 6 (sup

    SP - 157

    JO - Retrovirology

    T2 - Retrovirology

    JF - Retrovirology

    SN - 1742-4690

    ER -