Rodríguez Y, Santos A, Morera Y, Gerónimo H, Castro J, M;artínez R, Puente P, Arrieta CA, Silva R, Moro A, Perea SE, Martínez K, Ramos Y, Besada V, Llopiz A, Hardy E, Vázquez M, Guillén GE

Language: English
References: 12
Page: 1502-1503
PDF size: 279.23 Kb.

ABSTRACT

Interleukin (IL)-15 is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of rheumatoid arthritis (RA), a chronic inflammatory disease for which there is no effective therapy. In this report, we describe a novel vaccine based on active immunization with modified human IL-15 for the treatment of RA and others diseases related with IL-15 overexpression. The IL-15 obtained in E. coli exhibits a conformation of the disulfide bridges different to the one described for the native cytokine, which may favor the development of an immune response against this antigen. The results show that immunization with modified human IL-15 generates specific polyclonal antibodies against the cytokine in non-human primates, which suggests a rupture of B cells tolerance as consequence of immunization. These antibodies inhibited the biological activity of native IL-15 without affecting the human IL-2-induced proliferation of CTLL-2 cells, demonstrating the specificity of the antibodies by autologous IL-15. Additionally, we show that vaccination induces a regulated response of antibodies that neutralize the biological activity of simian IL-15, when aluminum hydroxide was used as adjuvant. The present work also provides the first safety elements of the anti-IL-15 vaccine in Macaca fascicularis monkeys, an animal model in which IL-15 shares a 97 % homology to the human molecule. This work received the Annual Award of the Cuban Academy of Sciences for the year 2017.

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