Chimeric Myostatin - Tetanic Toxin Epitopes and Heterologous Prime-boost Immunization Improve Immune Response Stimulating Muscle Growth in Mice

摘要

Myostatin is a transforming growth factor-beta family member who acts as a negative regulator of skeletal muscle growth. The interference of its biological activity could increase skeletal muscle growth with clinical and animal production applications. A strategy to block the myostatin action is by the induction of an immune response against it. In this work, we evaluated as an immunogen a recombinant myostatin fused to the tetanic toxin T- helper epitopes P2 and P30. Genetic constructs of the chimeric myostatin were cloned in an expression vector and used as a DNA vaccine. Besides, a chimeric genetic construct, P2-miostatin-P30 was expressed in Escherichia coli, obtaining a recombinant chimeric antigen. To find out the functionality of these genetic constructs as a vaccine in inducing muscle growth responses, experimental groups of BALB/c mice were DNA immunized with the myostatin fused to P2, P30 or both. Furthermore, to improve the immune response, a heterologous prime-boost immunization scheme was evaluated where the DNA inoculation was followed by immunization with the recombinant antigen P2-myostatin-P30. The different body segments weight was recorded in control and vaccinated mice groups, finding increased muscle masses in the vaccinated groups. These experiments showed the effectiveness of the P2 and P30 Thelper epitopes in inducing an immune response to the fused myostatin, leading to muscle growth. The heterologous prime-boost immunization protocol is a promising vaccination strategy reducing the time and amount of antigen used to induce a immune response to myostatin.