Poster: Herpes simplex vaccine vector co-expressing fused Mycobacterium Tuberculosis immunogens and Tat adjuvant enhances cellular and humoral responses in Balb/c mice

Tuberculosis (TB) caused by the intracellular Mycobacterium Tuberculosis (Mtb), is one of the major health problems in the world and responsible for about 2 million deaths annually. Currently Bacillus Calmette-Guerin (BCG) is the only TB vaccine available for humans. However BCG is the most controversial vaccine in use and its protective efficacy against adult TB is insufficient. To date several types of TB vaccines such as genetic modified BCG, protein-adjuvant combination, plasmid DNA and viral-based vaccines have been made and used in prime and boost strategies. In particular recombinant viral vectors expressing adjuvant molecules and Mtb fusion proteins that can generate a broader cellular and humoral response are highly promising candidates. 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. For this purpose, we have constructed viral vectors (HSVTB5Ag) that contain a gene cassette that express a fusion protein formed by 5 Mycobacterium tuberculosis 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. 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 (HSVTB5Ag/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. HSV-TB5Ag and HSV-TB5Ag/Tat vectors have been used to immunize Balb/C 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 cellular and humoral 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