Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates

• Published in: BMC immunology Vol. 17; no. 1; p. 30
• Main Authors: Rodríguez-Álvarez, Yunier, Morera-Díaz, Yanelys, Gerónimo-Pérez, Haydee, Castro-Velazco, Jorge, Martínez-Castillo, Rafael, Puente-Pérez, Pedro, Besada-Pérez, Vladimir, Hardy-Rando, Eugenio, Chico-Capote, Araceli, Martínez-Cordovez, Klaudia, Santos-Savio, Alicia
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.09.2016; BioMed Central
• Subjects: Analysis; Gene expression; Health aspects; Immunization; Immunology; Influence; Interleukin-15; Cuba; Neutralizing Abs; Immunization; CTLL-2 cells; Cytokine; IL-15; Non-human primates; Alum
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-016-0168-6

Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant. Immunization with mhIL-15 elicited a specific antibodies response that neutralized native IL-15-dependent biologic activity in a CTLL-2 cell proliferation assay. The highest neutralizing response was obtained in macaques immunized with mhIL-15 adjuvanted in Alum. This response, which was shown to be transient, also inhibited the activity of simian IL-15 and did not affect the human IL-2-induced proliferation of CTLL-2 cells. Also, in a pool of synovial fluid cells from two Rheumatoid Arthritis patients, the immune sera slightly inhibited TNF-α secretion. Finally, it was observed that this vaccine candidate neither affect animal behavior, clinical status, blood biochemistry nor the percentage of IL-15-dependent cell populations, specifically CD56 NK and CD8 T cells. Our results indicate that vaccination with mhIL-15 induced neutralizing antibodies to native IL-15 in non-human primates. Based on this fact, we propose that this vaccine candidate could be potentially beneficial for treatment of diseases where IL-15 overexpression is associated with their pathogenesis.