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BMC Immunology
Published in: BMC Immunology 1/2016

Open Access 01-12-2016 | Research article

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

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

Published in: BMC Immunology | Issue 1/2016

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Abstract

Background

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.

Results

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.

Conclusion

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.
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Metadata
Title
Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates
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
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2016
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-016-0168-6

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