Mucosal neutralising antibody vaccines against HIV/AIDS
The St George's Vaccine Institute is part of the €16.1M EURONEUT-41 European Commission 7th Framework Programme Integrated Project. The principal aim of this project is to establish a platform where gp41-derived vaccine candidates will be designed to elicit neutralising antibodies. Several families of immunogens which mimic gp41 in its fusion intermediate conformations are already available and others will be designed using modelling approaches. Candidates will be submitted to a thorough biophysical characterisation followed by a preclinical development in order to identify the most promising for clinical evaluation. A crucial selection parameter is the capacity of antigens to elicit neutralising antibodies using internationally standardized assays. Since sexual transmission accounts for more than 90% of HIV infection, the capacity of antibodies to inhibit infection at the mucosal level will also be determined.
In the final year of the project a formal clinical trial of a novel candidate will be performed by the St George's Vaccine Institute using a mucosal route of delivery.
In preparation for this a series of clinical and non-clinical studies are being conducted using model viral antigens (Human Papilloma Virus L antigens) delivered sublingually to determine whether sublingual antigen presentation has the same immunological phenotype as other mucosal routes (nasal, oral, vaginal) and in comparison with injected antigens. This study commenced in 2009 and recruitment has been completed. Final visit will be in June 2010. Results will explore the link between sublingual and vaginal immune systems for the first time in humans, using non-self adjuvanting molecules more representative of vaccine antigens.