HIV: the vaccine challenge

The Human Immunodeficiency Virus (HIV)/ AIDS is one of the greatest health challenges the world faces today. To date approximately 33.2 million people worldwide are living with HIV, from which 2.2 million are in Europe. An overwhelming majority of new infections are in developing countries where current anti-retroviral therapies are prohibitively expensive, and the impact of disease on both individuals and society is truly crippling. For infectious diseases vaccines remain the most effective and economic preventative therapies available. However despite significant efforts over the past decade to design new vaccines a truly effective HIV vaccine remains to be developed.

The Skin as a target for vaccination

The major innovative approach of CUT’HIVAC is to develop vaccine strategies across the skin and mucosa. Dr Behazine Combadiere and colleagues have previously demonstrated that vaccination by this route specifically activates the killer T cells (CD8) of the immune system.

Human skin; epidermis (blue) dermis (red)

These cells are believed to be crucial in combating the HIV virus and thus could be a crucial weapon of the immune system that can combat HIV-infected cells in infected individuals. Preferential induction of this arm of the immune system is achieved by targeting of skin antigen-presenting cells such as dermal dendritic cells and Langerhans cells. The skin is an organ rich in these cells, which are crucial for initiating an immune response. Equally important is that vaccination by these novel routes results in a strong antibody response in the mucosa (vagina, gut), which is often the site of initial HIV infection.

Needle-free vaccination

Human skin explants

The transcutaneous vaccination route also has a major advantage over other systems in that it is needle free. As areas of high infection such as sub Saharan Africa have limited medical infrastructure the advantage of a needle free vaccination strategy is enormous. It also removes the risk of infection caused by unsterile equipment.

Furthermore it is likely that to maintain a constant level of protective mucosal immunity repeated vaccinations would be required. A procedure such as the simple self-application of a vaccine over the skin makes this a feasible option in contrast to a vaccine requiring repeated injection by trained medical staff.

Clinical Trials

We have previously demonstrated the superior effectiveness of the transcutaneous route with influenza vaccines. We believe that this approach will also be applicable for HIV vaccines but we plan to demonstrate it by rapidly launching a Phase I clinical trial with healthy volunteers. In parallel we will also examine the transcutaneous route for therapeutic vaccination with a Phase I trial in HIV+ individuals. This will be performed in collaboration with the non-profit ORVACS (Objectif Recherche Vaccin SIDA) foundation in Paris. These early trials will greatly inform the development of the second round of clinical trials with next generation vaccine candidates, which will expand to incorporate our partners in the developing countries of Peru and Mozambique.

Next generation vaccines

A major challenge to the goal of a HIV vaccine is the rapid mutation of the virus and its subsequent evasion from the immune system. CUTHIVAC will utilize the latest DNA-GTU® vaccine technology developed by FITBiotech for its early clinical trials. This mimics the virus as it encodes the antigenic material in the host T-cell but importantly does not cause infection.

In addition new genetic sequences of HIV antigens (Gag/Pol and envelope proteins) will be designed for developed and developing countries, in order to propose innovative vaccine that will be tested for efficacy. Other adjuvant delivery systems will also be tested such as Heat shock proteins, virus like particles, and biodegradable nanoparticles. These compounds can all be delivered across the skin while stimulating subtly different immune responses thereby allowing us to tailor cut the required immune response to the disease in question. This will help to apply the knowledge gained from skin immunizations for HIV to other poverty related diseases such as malaria and HIV.

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