Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form

Aditya Pattani, Paul F McKay, Rhonda Curran, Joanne McCaffrey, Prem N Gupta, Deborah Lowry, Vicky L Kett, Robin J Shattock, Helen O McCarthy, R Karl Malcolm

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.
    LanguageEnglish
    Pages2778-2785
    JournalVaccine
    Volume30
    DOIs
    Publication statusPublished - 21 Feb 2012

    Fingerprint

    HIV Envelope Protein gp41
    Dosage Forms
    Immunization
    Antigens
    Vaccines
    Immunity
    Mucous Membrane
    Intravaginal Administration
    Cytokines
    Therapeutic Irrigation
    Subcutaneous Injections
    Recombinant Proteins
    Vaccination
    Proteins
    HIV
    Control Groups

    Cite this

    Pattani, A., McKay, P. F., Curran, R., McCaffrey, J., Gupta, P. N., Lowry, D., ... Malcolm, R. K. (2012). Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form. Vaccine, 30, 2778-2785. https://doi.org/10.1016/j.vaccine.2012.02.004
    Pattani, Aditya ; McKay, Paul F ; Curran, Rhonda ; McCaffrey, Joanne ; Gupta, Prem N ; Lowry, Deborah ; Kett, Vicky L ; Shattock, Robin J ; McCarthy, Helen O ; Malcolm, R Karl. / Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form. In: Vaccine. 2012 ; Vol. 30. pp. 2778-2785.
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    abstract = "A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.",
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    Pattani, A, McKay, PF, Curran, R, McCaffrey, J, Gupta, PN, Lowry, D, Kett, VL, Shattock, RJ, McCarthy, HO & Malcolm, RK 2012, 'Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form', Vaccine, vol. 30, pp. 2778-2785. https://doi.org/10.1016/j.vaccine.2012.02.004

    Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form. / Pattani, Aditya; McKay, Paul F; Curran, Rhonda; McCaffrey, Joanne; Gupta, Prem N; Lowry, Deborah; Kett, Vicky L; Shattock, Robin J; McCarthy, Helen O; Malcolm, R Karl.

    In: Vaccine, Vol. 30, 21.02.2012, p. 2778-2785.

    Research output: Contribution to journalArticle

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    AU - Gupta, Prem N

    AU - Lowry, Deborah

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