To employ two non-replicating delivery systems will be employed to deliver antigens to the immune system and to elicit the appropriate protective immune responses against human diseases such as HIV, HCV and tumours. The immune responses and their protective efficacy will be assessed in animal models. The mechanism of CTL activities of these particles and their ability to induce mucosal responses will be studied. Both particles will be further investigated and modified for broader application.
Two different self-assembled structures that lack nucleic acid have been developed as immunogen delivery systems during previous EEC funded projects. These are PPV-VLPs and NS1-TUBs and both have been shown to be highly immunogenic. Based on previous data we propose to generate chimeric VLPs and TUBs carrying a selection of T-cell epitopes of HIV-1, HCV and tumour antigens using recombinant baculovirus expression systems and insect cell cultures. Each assembled chimeric particles will be purified and characterised thoroughly at molecular and antigenic levels. Subsequently, these particles will be utilised to investigate their immunogenicity and their capabilities of inducing the appropriate immune responses in in vitro and in vivo model animals. The protective efficacy of each chimeric construct will be further assessed by challenge experiments in pre-clinical studies and for some constructs in clinical studies, if the opportunity becomes available. CTL response by non-replicating particles is a novel approach, and therefore the mechanism of such activity will be investigated in depth using the appropriate constructs. Lastly, each of the delivery systems will be modified by creating additional foreign sequence sites generating multiple chimeric copies by single recombinant vectors, and creating the delivery systems more immunologic by fusion with adjuvant, such as cholera toxin subunit. In addition, both types of particles will be subjected to high purified regimes suitable for human vaccine. The results and the reagents obtained from this project will allow to develop vaccines for other human and animal diseases.
Funding SchemeCSC - Cost-sharing contracts