Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms

Louise Donnelly, Rhonda M Curran, John S Tregoning, Paul F McKay, Tom Cole, Ryan J Morrow, Vicky L Kett, Gavin P Andrews, A David Woolfson, R Karl Malcolm, Robin J Shattock

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposure of CN54gp140 to the mucosal-associated lymphoid tissue of the female genital tract.
    LanguageEnglish
    Pages4512-4520
    JournalVaccine
    Volume29
    DOIs
    Publication statusPublished - 21 Apr 2011

    Fingerprint

    HIV-1
    Immunization
    Gels
    Intravaginal Administration
    Foams and Jellies Vaginal Creams
    Antigens
    Antibody Formation
    Vaccines
    AIDS Vaccines
    Drug Compounding
    Carboxymethylcellulose Sodium
    Freeze Drying
    Heterosexuality
    Lymphoid Tissue
    Primary Prevention
    HIV Infections
    glycoprotein gC, herpes simplex virus type 1
    Buffers
    Sodium
    Equipment and Supplies

    Cite this

    Donnelly, Louise ; Curran, Rhonda M ; Tregoning, John S ; McKay, Paul F ; Cole, Tom ; Morrow, Ryan J ; Kett, Vicky L ; Andrews, Gavin P ; Woolfson, A David ; Malcolm, R Karl ; Shattock, Robin J. / Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms. In: Vaccine. 2011 ; Vol. 29. pp. 4512-4520.
    @article{222d0fd80994438aa026643f9208a26d,
    title = "Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms",
    abstract = "Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol{\circledR} gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol{\circledR} gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposure of CN54gp140 to the mucosal-associated lymphoid tissue of the female genital tract.",
    author = "Louise Donnelly and Curran, {Rhonda M} and Tregoning, {John S} and McKay, {Paul F} and Tom Cole and Morrow, {Ryan J} and Kett, {Vicky L} and Andrews, {Gavin P} and Woolfson, {A David} and Malcolm, {R Karl} and Shattock, {Robin J}",
    year = "2011",
    month = "4",
    day = "21",
    doi = "10.1016/j.vaccine.2011.04.023",
    language = "English",
    volume = "29",
    pages = "4512--4520",
    journal = "Vaccine",
    issn = "0264-410X",
    publisher = "Elsevier",

    }

    Donnelly, L, Curran, RM, Tregoning, JS, McKay, PF, Cole, T, Morrow, RJ, Kett, VL, Andrews, GP, Woolfson, AD, Malcolm, RK & Shattock, RJ 2011, 'Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms', Vaccine, vol. 29, pp. 4512-4520. https://doi.org/10.1016/j.vaccine.2011.04.023

    Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms. / Donnelly, Louise; Curran, Rhonda M; Tregoning, John S; McKay, Paul F; Cole, Tom; Morrow, Ryan J; Kett, Vicky L; Andrews, Gavin P; Woolfson, A David; Malcolm, R Karl; Shattock, Robin J.

    In: Vaccine, Vol. 29, 21.04.2011, p. 4512-4520.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Intravaginal immunization using the recombinant HIV-1 clade-C trimericenvelope glycoprotein CN54gp140 formulated within lyophilized soliddosage forms

    AU - Donnelly, Louise

    AU - Curran, Rhonda M

    AU - Tregoning, John S

    AU - McKay, Paul F

    AU - Cole, Tom

    AU - Morrow, Ryan J

    AU - Kett, Vicky L

    AU - Andrews, Gavin P

    AU - Woolfson, A David

    AU - Malcolm, R Karl

    AU - Shattock, Robin J

    PY - 2011/4/21

    Y1 - 2011/4/21

    N2 - Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposure of CN54gp140 to the mucosal-associated lymphoid tissue of the female genital tract.

    AB - Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposure of CN54gp140 to the mucosal-associated lymphoid tissue of the female genital tract.

    U2 - 10.1016/j.vaccine.2011.04.023

    DO - 10.1016/j.vaccine.2011.04.023

    M3 - Article

    VL - 29

    SP - 4512

    EP - 4520

    JO - Vaccine

    T2 - Vaccine

    JF - Vaccine

    SN - 0264-410X

    ER -