Recent major breakthroughs in the field of HSV-1 technology authorize and support the use of HSV-1 based vectors as vaccine vectors against HSV-1 infection or for the delivery of foreign antigens. One of the major obstacles in developing effective vaccines against intracellular pathogens is the incomplete understanding on the mechanisms that contribute to effective immune responses. The identification of a new class of adjuvants, expressed by HSV vectors, able to direct and broad antigen presentation by the major histocompatibility complexes (MHC) can be used to achieve a stronger effect or a more potent skewing of immune responses. The focus of our laboratory is to develop vaccines able to activate and modulate effective immune responses not only against HSV but also against other intracellular pathogens such as Mycobacterium tuberculosis (Mtb). In this context, we have investigated, whether HIV-1 Tat protein co-expressed with HSV-1 vector antigens, may act as a molecule capable to induce such broad and protective immunity against intracellular pathogens. The concept of Tat as a candidate adjuvant has derived from in vitro and in vivo evidences indicating that the biologically active clade B Tat protein possesses several immunomodulatory features making it an attractive adjuvant for other antigens and suggesting that it can be exploited for vaccination strategies and therapeutic interventions aimed at modulating antigen-specific immune responses in different types of human diseases. In recent studies we have demonstrated that an attenuated replication competent HSV vector expressing Tat, as immunostimulatory molecule, is immunogenic and confers protection in mice challenged with a lethal dose of wild-type HSV1. Moreover, in preliminary experiments using a non-replicative HSV vector expressing Mtb antigens and Tat we observed that Tat can function as a potent adjuvant that modulates the CTL epitope hierarchy and broadens the epitope-specific T cell responses of heterologous antigens. Our results suggest that HSV vector backbone co-expressing an adjuvant molecule is able to broaden epitope responses and that this can be a new concept for a future vaccine against intracellular pathogens.
Comunicazione orale, Keynote speaker: Herpes Simplex Vector Expressing Hiv1 Tat: A New Strategy For Vaccine Development
MARCONI, Peggy Carla Raffaella
2014
Abstract
Recent major breakthroughs in the field of HSV-1 technology authorize and support the use of HSV-1 based vectors as vaccine vectors against HSV-1 infection or for the delivery of foreign antigens. One of the major obstacles in developing effective vaccines against intracellular pathogens is the incomplete understanding on the mechanisms that contribute to effective immune responses. The identification of a new class of adjuvants, expressed by HSV vectors, able to direct and broad antigen presentation by the major histocompatibility complexes (MHC) can be used to achieve a stronger effect or a more potent skewing of immune responses. The focus of our laboratory is to develop vaccines able to activate and modulate effective immune responses not only against HSV but also against other intracellular pathogens such as Mycobacterium tuberculosis (Mtb). In this context, we have investigated, whether HIV-1 Tat protein co-expressed with HSV-1 vector antigens, may act as a molecule capable to induce such broad and protective immunity against intracellular pathogens. The concept of Tat as a candidate adjuvant has derived from in vitro and in vivo evidences indicating that the biologically active clade B Tat protein possesses several immunomodulatory features making it an attractive adjuvant for other antigens and suggesting that it can be exploited for vaccination strategies and therapeutic interventions aimed at modulating antigen-specific immune responses in different types of human diseases. In recent studies we have demonstrated that an attenuated replication competent HSV vector expressing Tat, as immunostimulatory molecule, is immunogenic and confers protection in mice challenged with a lethal dose of wild-type HSV1. Moreover, in preliminary experiments using a non-replicative HSV vector expressing Mtb antigens and Tat we observed that Tat can function as a potent adjuvant that modulates the CTL epitope hierarchy and broadens the epitope-specific T cell responses of heterologous antigens. Our results suggest that HSV vector backbone co-expressing an adjuvant molecule is able to broaden epitope responses and that this can be a new concept for a future vaccine against intracellular pathogens.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
