Our proposal is to combine the Tat protein, which role as adjuvant has already been proved, with Mycobacterium tuberculosis antigens in the contest of Herpes simplex virus type 1 (HSV-1) vector vaccines to fight TB infections. This project will also include studies addressed to improve the vector technology and knowledge, to develop better, safer, and more efficient vector vaccines against opportunistic infections. More precisely, we propose to construct polyantigenic vaccines based on HSV-1 recombinant vectors that will simultaneously express Tat and several mycobacterial antigens (e.g.: ESAT6, Ag85B etc), to induce a more complete pattern of immune responses. These vectors express only a restricted set of proteins and, as a consequence, they are disarmed and/or are less able than wild type HSV-1 to counteract the cellular defence mechanisms (particularly those mediated by interferons and apoptotic pathways and, more generally, to innate defence mechanisms). Despite the fact that our previous generations of vector vaccines induce CTL-responses and protection, we will study how Tat protein, expressed by the vectors, can broad the epitope- specific T cell responses not only against the model transgene (TB antigens) but also against HSV antigens, increasing the vaccine efficacy in TB and HSV challenge animal models. These results may have many applications since the search for new adjuvant molecules for vaccine formulations is still a main goal in vaccinology.

Viral vector expressing Tat as an immunomodulatory molecule represents a new vaccine strategy for opportunistic infections

MARCONI, Peggy Carla Raffaella
2009

Abstract

Our proposal is to combine the Tat protein, which role as adjuvant has already been proved, with Mycobacterium tuberculosis antigens in the contest of Herpes simplex virus type 1 (HSV-1) vector vaccines to fight TB infections. This project will also include studies addressed to improve the vector technology and knowledge, to develop better, safer, and more efficient vector vaccines against opportunistic infections. More precisely, we propose to construct polyantigenic vaccines based on HSV-1 recombinant vectors that will simultaneously express Tat and several mycobacterial antigens (e.g.: ESAT6, Ag85B etc), to induce a more complete pattern of immune responses. These vectors express only a restricted set of proteins and, as a consequence, they are disarmed and/or are less able than wild type HSV-1 to counteract the cellular defence mechanisms (particularly those mediated by interferons and apoptotic pathways and, more generally, to innate defence mechanisms). Despite the fact that our previous generations of vector vaccines induce CTL-responses and protection, we will study how Tat protein, expressed by the vectors, can broad the epitope- specific T cell responses not only against the model transgene (TB antigens) but also against HSV antigens, increasing the vaccine efficacy in TB and HSV challenge animal models. These results may have many applications since the search for new adjuvant molecules for vaccine formulations is still a main goal in vaccinology.
2009
Marconi, Peggy Carla Raffaella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1530376
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