Construção de vírus recombinante na plataforma MVA expressando peptídeos HBZ do HTLV-1: geração de candidatos à vacina terapêutica

Abstract

Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus that infects about 5 to 10 million people worldwide. Brazil is an endemic country for HTLV-1 and there are about 2,5 million people infected, which represents the region with the highest number of people infected in the world. The virus infects primarily CD4+ T cells and it is able to stablish a chronic infection that can result in distinct outcomes. The majority of the carriers are asymptomatic, however about 5% of them will develop pathologies related to the infection, such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 express some regulatory proteins, which are crucial in the development of the pathogenesis and chronification of the infection, highlighting the HBZ protein. This protein can promote cell proliferation and host immune response evasion, which result in viral persistence and disease progression. Despite the importance of the HTLV-1, there are not safe and efficient therapies to treat and control the infection. Thus, this work proposes to develop a potential therapeutic candidate to HTLV-1, based on viral vectors. Based on in silico analysis and in the literature, HBZ immunogenic epitopes that can induce cellular immune response were identified, these are hypothetically capable of inducing HBZ-specific cytotoxic T cells and lysing the infected cell, in this way, controlling the infection and blocking or reducing the disease progression. Therefore, two gene cassettes coding multiepitope proteins were designed containing the identified epitopes, a signal peptide was added in one of the cassettes. The therapeutic vaccine design was based on the viral vector Modified Vaccinia virus Ankara (MVA), a promising vector used in vaccine development. The constructions were successfully generated, the viruses were expanded and confirmed through sequencing.