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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Effect of sera from Alum group on IL-2-dependent proliferative activity in CTLL-2 cells. Cells were cultured in presence of IL-2, IL-2 plus serial dilutions of sera (starting dilution 1:25), IL-2 plus serial dilutions of an anti-human IL-2 Ab or medium. Cell proliferation was evaluated by MTT staining. All tested sera correspond to 15 days after the third immunization
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5036325&req=5

Fig6: Effect of sera from Alum group on IL-2-dependent proliferative activity in CTLL-2 cells. Cells were cultured in presence of IL-2, IL-2 plus serial dilutions of sera (starting dilution 1:25), IL-2 plus serial dilutions of an anti-human IL-2 Ab or medium. Cell proliferation was evaluated by MTT staining. All tested sera correspond to 15 days after the third immunization

Mentions: To study the specificity of the neutralizing activity of sera obtained from the Alum group, we assessed their effects on human IL-2-induced proliferation of CTLL-2 cells. As observed in Fig. 6, the Abs generated after mhIL-15-based immunization had no effect on human IL-2-induced proliferation of CTLL-2 cells; while the commercial neutralizing anti-human IL-2 Ab exhibited a dose-dependent inhibition.Fig. 6


Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates
Effect of sera from Alum group on IL-2-dependent proliferative activity in CTLL-2 cells. Cells were cultured in presence of IL-2, IL-2 plus serial dilutions of sera (starting dilution 1:25), IL-2 plus serial dilutions of an anti-human IL-2 Ab or medium. Cell proliferation was evaluated by MTT staining. All tested sera correspond to 15 days after the third immunization
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036325&req=5

Fig6: Effect of sera from Alum group on IL-2-dependent proliferative activity in CTLL-2 cells. Cells were cultured in presence of IL-2, IL-2 plus serial dilutions of sera (starting dilution 1:25), IL-2 plus serial dilutions of an anti-human IL-2 Ab or medium. Cell proliferation was evaluated by MTT staining. All tested sera correspond to 15 days after the third immunization
Mentions: To study the specificity of the neutralizing activity of sera obtained from the Alum group, we assessed their effects on human IL-2-induced proliferation of CTLL-2 cells. As observed in Fig. 6, the Abs generated after mhIL-15-based immunization had no effect on human IL-2-induced proliferation of CTLL-2 cells; while the commercial neutralizing anti-human IL-2 Ab exhibited a dose-dependent inhibition.Fig. 6

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus