Patterson Vaccine Discovery Consortium (VDC)

 

The major goal of the project is to develop a HIV CD8⁺ T cell vaccine targeted to dendritic cells in the skin that will induce a broad CTL response, and to test our hypothesis in a repeated low dose challenge model. 

In the original proposal we aimed to develop a micro-needle patch composed of dried sugars and our adenovirus vaccine vectors, which would deliver the “vaccine” to the skin dendritic cells intradermally.  Experiments have identified the cells targeted by this delivery system and shown that it can successfully induce a CD8 T cell response.  Our data indicate that delivery of the “vaccine” is affected by the shape of the micro-needle, with pyramid shaped needles being more effective at penetrating the skin than cone shaped needles. 

However, further research and development of the micro-needle patch system is still required, and thus delivery of the “vaccine” in the repeated low dose challenge study will be done using Becton Dickinson Technologies intradermal delivery system Microcone™.  This device is available to the consortium following successful collaborative negotiations.  The Microcone™ represents BD Technologies R&D model of the commercially developed Micro Injection System™ licensed by sanofi pasteur for use with their influenza vaccine. 

To address the aim of improving the magnitude and breadth of the CD8 T cell response, we have employed two strategies; 

• Firstly the gag gene has been fused with ubiquitin to increase proteasome processing
• Secondly a series of Adenovirus vectors have been constructed each containing a different fragment of the gag gene with the aim of avoiding competition on the surface of the antigen presenting cell between different clones of T cells that are specific for different gag epitopes. 

Fusion protein constructs tested have showed more effective targeting of gag to the proteasome than than unmodified gag.  However, there was no improvement in the magnitude of gag-specific CD8 T cell responses induced when compared with unmodified gag genes.  There are several possibilities to explain these results and we are currently working on strategies to overcome this problem.

 

 

The project is led by Imperial College London (PI: Dr Steve Patterson) in collaboration with King’s College London (Dr Linda Klavinkis), Royal Holloway University of London (Prof George Dickson), NIBSC (Dr Neil Almond), Hybrid Systems Ltd, and TheraJect Inc .  The original press release for this award can be found here. 

For further information please contact Dr Andrea Meiser (Project Manager)

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