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Immunogenicity profile in African green monkeys of a vaccine candidate based on a mutated form of human Interleukin-15.
Rodríguez-Álvarez, Yunier; Batista-Roche, Lino Gerardo; Llopiz-Arzuaga, Alexey; Puente-Pérez, Pedro; Martínez-Castillo, Rafael; Castro-Velazco, Jorge; Santos-Savio, Alicia.
Afiliação
  • Rodríguez-Álvarez Y; Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba. yunier.rodriguez@cigb.edu.cu.
  • Batista-Roche LG; Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
  • Llopiz-Arzuaga A; Chemistry and Physics Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
  • Puente-Pérez P; Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
  • Martínez-Castillo R; Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
  • Castro-Velazco J; Animal Facility Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
  • Santos-Savio A; Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, Avenue 31, PO Box 6162, 10 600, Havana, Cuba.
BMC Immunol ; 22(1): 79, 2021 12 18.
Article em En | MEDLINE | ID: mdl-34922462
BACKGROUND: Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based on the recombinant modified human IL-15 (mhIL-15) mixed with the alum adjuvant. A previous study in non-human primates Macaca fascicularis has shown that vaccination induces neutralizing antibodies against native IL-15, without affecting animal behavior, clinical status, or the percentage of IL-15-dependent cell populations. However, the mhIL-15 used as an antigen was active in the IL-2-dependent cytotoxic T-cell line CTLL-2, which could hinder its therapeutic application. The current article evaluated the immunogenicity in African green monkeys of a vaccine candidate based on IL-15 mutant D8SQ108S, an inactive form of human IL-15. RESULTS: IL-15 D8SQ108S was inactive in the CTLL-2 bioassay but was able to competitively inhibit the biological activity of human IL-15. Immunization with 200 µg of IL-15 mutant combined with alum elicited anti-IL-15 IgG antibodies after the second and third immunizations. The median values of anti-IL-15 antibody titers were slightly higher than those generated in animals immunized with 200 µg of mhIL-15. The highest antibody titers were induced after the third immunization in monkeys vaccinated with 350 µg of IL-15 D8SQ108S. In addition, sera from immunized animals inhibited the biological activity of human IL-15 in CTLL-2 cells. The maximum neutralizing effect was observed after the third immunization in sera of monkeys vaccinated with the highest dose of the IL-15 mutant. These sera also inhibited the proliferative activity of simian IL-15 in the CTLL-2 bioassay and did not affect the IL-2-induced proliferation of the aforementioned T-cell line. Finally, it was observed that vaccination neither affects the animal behavior nor the general clinical parameters of immunized monkeys. CONCLUSION: Immunization with inactive IL-15 D8SQ108S mixed with alum generated neutralizing antibodies specific for human IL-15 in African green monkeys. Based on this fact, the current vaccine candidate could be more effective than the one based on biologically active mhIL-15 for treating autoimmune disorders involving an uncontrolled overproduction of IL-15.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas / Linfócitos T / Interleucina-15 Limite: Animals / Humans Idioma: En Revista: BMC Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Cuba País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas / Linfócitos T / Interleucina-15 Limite: Animals / Humans Idioma: En Revista: BMC Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Cuba País de publicação: Reino Unido