Tuberculosis (TB), even is preventable and curable, still represents a major challenge for public health and has been considered and declared a global emergency by the WHO due to the immense medical/societal costs involved in the disease, highlighting the urgent need for the development and deployment of an effective vaccine. The consensus of the TB research and clinical community is that the current TB epidemic will not stop without a new and more efficacious vaccine to reduce the pool of infectious people transmitting their disease prior to therapy. The main goal of our study was to explore and develop new efficacious and safe Herpes simplex type 1 (HSV-1) vector based vaccines against TB due to the inconsistent protection efficacy of Bacille Calmette-Guèrin (BCG) immunization. For this purpose, we have constructed viral vectors (HSV::TB5Ag) that contain a gene cassette that express a fusion protein formed by 5 Mycobacterium tuberculosis (Mtb) antigens (TB5Ag: Ag85B, ESAT-6, Mpt 64/63/83) that have been reported to act as efficient activators of the protective immune-responses against Mtb (Delogu, Li et al. 2002). In order to modulate and increase Th1 and/or Th2 responses against a broader range of the Mtb fusion protein epitopes we construct an HSV vector co-expressing TB5Ag and HIV-1 Tat protein as immune-modulator (HSV::TB5Ag/Tat). At this regard we have previously reported the capacity of Tat to reveal new epitopes and to induce protective cellular immune responses against HSV1 lethal infection in a mice model (Marconi submitted publication). HSV::TB5Ag and HSV::TB5Ag/Tat vectors have been used to immunize BalbC mice with different protocols of immunization. The group of mice vaccinated with the vector co-expressing TB5Ag and HIV-1 Tat, compared with mice immunized with the vector expressing only TB5Ag, have shown a broader epitopes specific T cell responses. These data strengthen the hypothesis that Tat acts as a potent adjuvant since modulates Th1 and Th2 epitopes hierarchy. The results from the in vivo experiments indicate that HSV::TB5Ag/Tat vector is a potential candidate vaccine against Mtb for further studies on TB protection
Comunicazione orale, KN: A New Vaccine Approach To Fight Mycobacterium Tuberculosis
MARCONI, Peggy Carla Raffaella;SICURELLA, Mariaconcetta;CECCHI, Damiano;MANSERVIGI, Roberto
2014
Abstract
Tuberculosis (TB), even is preventable and curable, still represents a major challenge for public health and has been considered and declared a global emergency by the WHO due to the immense medical/societal costs involved in the disease, highlighting the urgent need for the development and deployment of an effective vaccine. The consensus of the TB research and clinical community is that the current TB epidemic will not stop without a new and more efficacious vaccine to reduce the pool of infectious people transmitting their disease prior to therapy. The main goal of our study was to explore and develop new efficacious and safe Herpes simplex type 1 (HSV-1) vector based vaccines against TB due to the inconsistent protection efficacy of Bacille Calmette-Guèrin (BCG) immunization. For this purpose, we have constructed viral vectors (HSV::TB5Ag) that contain a gene cassette that express a fusion protein formed by 5 Mycobacterium tuberculosis (Mtb) antigens (TB5Ag: Ag85B, ESAT-6, Mpt 64/63/83) that have been reported to act as efficient activators of the protective immune-responses against Mtb (Delogu, Li et al. 2002). In order to modulate and increase Th1 and/or Th2 responses against a broader range of the Mtb fusion protein epitopes we construct an HSV vector co-expressing TB5Ag and HIV-1 Tat protein as immune-modulator (HSV::TB5Ag/Tat). At this regard we have previously reported the capacity of Tat to reveal new epitopes and to induce protective cellular immune responses against HSV1 lethal infection in a mice model (Marconi submitted publication). HSV::TB5Ag and HSV::TB5Ag/Tat vectors have been used to immunize BalbC mice with different protocols of immunization. The group of mice vaccinated with the vector co-expressing TB5Ag and HIV-1 Tat, compared with mice immunized with the vector expressing only TB5Ag, have shown a broader epitopes specific T cell responses. These data strengthen the hypothesis that Tat acts as a potent adjuvant since modulates Th1 and Th2 epitopes hierarchy. The results from the in vivo experiments indicate that HSV::TB5Ag/Tat vector is a potential candidate vaccine against Mtb for further studies on TB protectionI documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
