Title |
Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates
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Published in |
BMC Immunology, September 2016
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DOI | 10.1186/s12865-016-0168-6 |
Pubmed ID | |
Authors |
Yunier Rodríguez-Álvarez, Yanelys Morera-Díaz, Haydee Gerónimo-Pérez, Jorge Castro-Velazco, Rafael Martínez-Castillo, Pedro Puente-Pérez, Vladimir Besada-Pérez, Eugenio Hardy-Rando, Araceli Chico-Capote, Klaudia Martínez-Cordovez, Alicia Santos-Savio |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 7 | 23% |
Student > Ph. D. Student | 4 | 13% |
Other | 3 | 10% |
Student > Doctoral Student | 2 | 7% |
Student > Master | 2 | 7% |
Other | 5 | 17% |
Unknown | 7 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 33% |
Biochemistry, Genetics and Molecular Biology | 4 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
Unspecified | 2 | 7% |
Immunology and Microbiology | 2 | 7% |
Other | 1 | 3% |
Unknown | 8 | 27% |