RESUMO
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.
Assuntos
Interleucina-15/imunologia , Linfócitos T/imunologia , Vacinas/imunologia , Compostos de Alúmen , Animais , Anticorpos Neutralizantes/metabolismo , Proliferação de Células , Chlorocebus aethiops , Citotoxicidade Imunológica , Humanos , Imunização , Imunogenicidade da Vacina , Interleucina-15/genética , Camundongos , Mutação/genéticaRESUMO
This study was performed to investigate the potential asymptomatic Leptospira reservoir status among African green monkeys (AGMs) in the Caribbean island of Saint Kitts, and whether there is any renal pathology associated with Leptospira exposure. Forty-eight percent of AGMs tested were positive for Leptospira antibodies by the microscopic agglutination test. Leptospira DNA was detected in 4% of kidney samples tested using a lipl32 gene based PCR. We observed minimal to severe microscopic renal lesions in 85% of the AGM kidneys evaluated. The majority of the AGMs (n = 26) had only minimal to mild interstitial nephritis and a few (n = 3) had moderate to severe lesions. The presence of interstitial nephritis was not significantly associated with Leptospira exposure. The presence of infected AGMs in a small surface limited geographic region may pose zoonotic threat to humans and animals. The impact of Leptospira infection in renal pathology in AGMs warrants further investigation. AGMs residing in a natural setting in an insular, surface limited Leptospira endemic geographic region may offer opportunities for comparative studies to advance the field of leptospirosis. Due to their similarity to humans, such studies in AGMs may also provide translational opportunities to advance Leptospira research.
RESUMO
BACKGROUND: Some factors such as sex, age, and captivity conditions have a direct influence on the normal hematological and serum biochemical parameters of African green monkeys. On the other hand, reliability in reported values is in many cases limited by studied animal number (<200) and there is not report on the correlation of these parameters with the age in each sex animal group. Thus, this study sought determining normal hematological (11) and serum biochemical parameters (9) of 400 captive housed African green monkeys and also correlate them with the age of the animals. METHODS: A total of 200 females and 200 males were grouped by the sex and age groups (1-2, 3-4, 5-6, and 7-8 years old) for measuring normal values of hematological and serum biochemical parameters and to study the correlation of these parameters with the age of the animals. RESULTS: As key outcome, the main hematological and serum biochemical reference values of African green monkeys were determined. Significant differences (P < 0.05) were found among 95% of studied parameters between males and females. About 75% and 95% of the parameters were influenced by the age in the female and male groups, respectively. About 35% of hematological and serum biochemical parameters correlated positively (R(2) > 0.5) with the age in the female monkeys. On the contrary in the male monkeys, only 45% of parameters correlated positively with the age (R(2) > 0.5). CONCLUSIONS: Thus, authors believe that results of this study are important for assisting researchers in the assessment of health status of captive housed African green monkeys for preclinical studies.
Assuntos
Envelhecimento/sangue , Animais de Laboratório/sangue , Chlorocebus aethiops/sangue , Fatores Etários , Animais , Análise Química do Sangue/veterinária , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/veterinária , Estudos de Coortes , Feminino , Testes Hematológicos/veterinária , Abrigo para Animais/classificação , Masculino , Valores de Referência , Fatores SexuaisRESUMO
OBJECTIVE: This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. METHODS: Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. RESULTS: Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. CONCLUSIONS: We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu.