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

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

Pattani, Aditya, McKay, Paul F, Curran, Rhonda, McCaffrey, Joanne, Gupta, Prem N, Lowry, Deborah, Kett, Vicky L, Shattock, Robin J, McCarthy, Helen O and Malcolm, R Karl (2012) Molecular investigations into vaginal immunization with HIV gp41 antigenicconstruct H4A in a quick release solid dosage form. Vaccine, 30 . pp. 2778-2785. [Journal article]

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DOI: 10.1016/j.vaccine.2012.02.004

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.

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:23178
Deposited By:Dr Rhonda Curran
Deposited On:31 Aug 2012 12:00
Last Modified:31 Aug 2012 12:00

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