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

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. © 2012 Elsevier Ltd. All rights reserved.

PRELIMINARY INVESTIGATIONS CONCERNING THE ANTI-ADHERENCE PROPERTIES OF POLYHEXAMETHYLENEBIGUANIDE (VANTOCIL IB(TM))

The effect of polyhexamethylenebiguanide (PHMB) on adherence of Candida albicans blastospores to human buccal epithelial cells (BEG) was examined in vitro. Treatments of either blastospores or BEC with PHMB (50 and 1000 mu g ml(-1)) significantly reduced the number of adherent blastospores per BEC and increased the number of BEC devoid of blastospores.

A Bayesian network hybrid model for representing accident and emergency waiting times

The paper introduces a new modeling approach that represents the waiting times in an accident and emergency (A&E) department in a UK based national health service (NHS) hospital. The technique uses Bayesian networks to capture the heterogeneity of arriving patients by representing how patient covariates interact to influence their waiting times in the department. Such waiting times have been reviewed by the NHS as a means of investigating the efficiency of A&E departments (emergency rooms) and how they operate. As a result activity targets are now established based on the patient total waiting times with much emphasis on trolley waits.

Virtual Engineering Centre - Examples of Virtual Prototyping and Multidisciplinary Design Optimization

The requirement for the use of Virtual Engineering, encompassing the construction of Virtual Prototypes using Multidisciplinary Design Optimisation, for the development of future aerospace platforms and systems is discussed. Some of the activities at the Virtual Engineering Centre, a University of Liverpool initiative, are described and a number of case studies involving a range of applications of Virtual Engineering illustrated.

Effectiveness of multidisciplinary early rehabilitation in reducing behaviour-related risk factors

To evaluate the effect of a 4-week primary prevention programme on health-risk behaviours amongst employees at increased risk of work incapacity.