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


CONCLUSIONS
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.
Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10 600, Cuba. yunier.rodriguez@cigb.edu.cu.
Yunier
Y
Rodríguez-Álvarez
Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10 600, Cuba.
Yanelys
Y
Morera-Díaz
Quality Control Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10600, Cuba.
Haydee
H
Gerónimo-Pérez
Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10600, Cuba.
Jorge
J
Castro-Velazco
Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10600, Cuba.
Rafael
R
Martínez-Castillo
Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10600, Cuba.
Pedro
P
Puente-Pérez
Chemistry and Physics Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10600, Cuba.
Vladimir
V
Besada-Pérez
Biotechnology Laboratory, Study Center for Research and Biological Evaluations, Institute of Pharmacy and Foods, Havana University, Avenue 222, PO Box 13600, Havana, 10600, Cuba.
Eugenio
E
Hardy-Rando
Rheumatology Department, Hermanos Ameijeiras Hospital, San Lazaro 701, PO Box 6122, Havana, 10600, Cuba.
Araceli
A
Chico-Capote
Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10 600, Cuba.
Klaudia
K
Martínez-Cordovez
Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, Havana, 10 600, Cuba.
Alicia
A
Santos-Savio
Alum; CTLL-2 cells; Cytokine; IL-15; Immunization; Neutralizing Abs; Non-human primates
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