Toxicidad a dosis repetida e inmunogenicidad en Cercopithecus aethiops, del candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo / Repeated dose toxicity and immunogenicity in Cercopithecus aethiops of SARS-CoV-2 SOBERANA 01 (FINLAY-FR-01) vaccine candidate

En el Instituto Finlay de Vacunas se desarrolló el candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo. Este trabajo tuvo como objetivo evaluar la inmunogenicidad y posibles efectos toxicológicos del candidato vacunal SOBERANA 01 (FINLAY-FR-01 en Cercopithecus aethiops. Se utilizaron cinco primates no humanos (hembras), de 1-3 años de edad y 1-4 kg de peso corporal, distribuidos en dos grupos experimentales: Control (Solución Salina Fisiológica) y Tratado SOBERANA 01 (FINLAY-FR-01). El estudio se extendió por 84 días, en un esquema a dosis repetida de cuatro inmunizaciones los días 0, 28, 56 y 70. Se realizaron observaciones clínicas diarias, peso corporal, signos vitales (temperatura rectal, frecuencia respiratoria, y frecuencia cardíaca), exámenes electrocardiográficos, toma de la temperatura del sitio de inyección, musculometría e irritabilidad dérmica. Fueron realizados exámenes de hematología, bioquímica sanguínea, así como estudios inmunológicos. El ensayo concluyó con una supervivencia del 100por ciento, no se manifestaron signos de toxicidad, no hubo variaciones hematológicas, ni de la bioquímica sanguínea asociadas a la sustancia de ensayo. Además, no se observaron efectos locales en el sitio de administración. Por último, el candidato vacunal resultó inmunogénico, ya que se indujeron títulos altos de IgG anti-RBD, así como de la inhibición de la unión de RBD a ACE2(AU)

At Finlay Vaccine Institute has been developed the vaccine candidate SOBERANA 01 (FINLAY-FR-01) against SARS-CoV-2 virus, causing COVID-19. This work aims to evaluate the immunogenicity and possible toxicological effects of the SOBERANA 01 (FINLAY-FR-01) vaccine candidate in Cercopithecus aethiops. Five non-human primates (females) from 1-3 years old and 1-4 kg of body weight were distributed in two experimental groups: Control (Physiological Saline Solution) and Treated (SOBERANA 01 FINLAY-FR-01). The study extended through 84 days, in a repeated dose schedule of four immunizations on days 0, 28, 56, and 70. Daily clinical observations, body weight, vital signs (rectal temperature, respiratory rate, and heart rate), electrocardiographic examinations, temperature of the injection site, musculometry and dermic irritability, were performed. Hematological and blood biochemistry tests, as well as immunological studies were assessed. At the end of the assay 100percent survival was obtained, there were no signs of toxicity neither hematological or blood biochemistry variations associated with the test substance. In addition, no local effects were observed at the administration site. Finally, the vaccine candidate was immunogenic, since high titers of anti-RBD IgG, as well as inhibition of the RBD to ACE2 binding were induced(AU)

Benefits of D-005, a lipid extract from Acrocomia crispa fruits, in the prevention of acute kidney njury induced by nephrotoxicity in rats / Benefícios do D-005, um extrato lipídico de frutos da Acrocomia crispa, na prevenção de lesão renal aguda induzida por nefrotoxicidade em ratos

Abstract Introduction: Aminoglycoside-induced acute kidney injury (AKI) is a pathology closely linked to oxidative and inflammatory reactions. Taking into account the previous reported antioxidant and anti-inflammatory effects of D-005, a lipid extract obtained from Cuban palm Acrocomia crispa (Arecaceae) fruits, this work aimed to evaluate the effects of D-005 on kanamycin-induced AKI. Methods: Male Wistar rats were divided into 7 groups: negative control (vehicle, Tween 65/H2O) and six groups treated with kanamycin to induce AKI: positive control (vehicle), D-005 (25, 100, 200, and 400 mg/kg) and grape seed extract (GSE, 200 mg/kg). D-005, vehicle, and GSE oral treatments were administered once daily for seven days, 1 h before kanamycin (500 mg/kg, i.p.). Serum uric acid and urea concentrations, renal histopathology, and oxidative markers (malondialdehyde (MDA), sulfhydryl (SH) groups, and catalase (CAT) activity) were assessed. Results: D-005 significantly reduced uric acid and urea levels, starting from D-005 100 mg/kg. Histopathologically, D-005, at all the tested doses, protected renal parenchyma structures (glomeruli, proximal tubules, and interstitium). These findings were accompanied by a significant reduction of MDA and SH group concentrations as well as restoration of CAT activity. The highest percentages of inhibition were obtained with the dose of 400 mg/kg. GSE, the reference substance, also prevented kanamycin-induced biochemical and histopathological changes, as well as reduced MDA and SH groups and restored CAT activity. Conclusion: The administration of repeated oral doses of D-005 significantly protected against kanamycin-induced AKI, which could be associated with the antioxidant and anti-inflammatory effects of this extract.

Resumo Introdução: Lesão renal aguda induzida por aminoglicosídeos é uma patologia intimamente ligada a reações oxidativas e inflamatórias. Considerando efeitos antioxidantes e anti-inflamatórios relatados anteriormente do D-005, um extrato lipídico de frutos da palmeira cubana Acrocomia crispa (Arecaceae), este trabalho avaliou efeitos do D-005 na LRA induzida por canamicina. Métodos: Dividiu-se ratos Wistar machos em 7 grupos: controle negativo (veículo, Tween 65/H2O) e seis grupos tratados com canamicina para induzir LRA: controle positivo (veículo), D-005 (25, 100, 200, 400 mg/kg) e extrato de semente de uva (ESU, 200 mg/kg). D-005, veículo, e tratamentos orais com ESU foram administrados uma vez por dia durante sete dias, 1 h antes da canamicina (500 mg/kg, i.p.). Avaliou-se concentrações séricas de ácido úrico e ureia, histopatologia renal e marcadores oxidativos (malondialdeído (MDA), grupos sulfidrila (SH), atividade de catalase (CAT)). Resultados: D-005 reduziu significativamente níveis de ácido úrico e ureia, partindo de D-005 100 mg/kg. Histopatologicamente, D-005, em todas as doses testadas, protegeu estruturas do parênquima renal (glomérulos, túbulos proximais e interstício). Estes achados foram acompanhados por uma redução significativa das concentrações de MDA e grupo SH, e pela restauração da atividade CAT. As maiores porcentagens de inibição foram obtidas com a dose de 400 mg/kg. ESU, a substância de referência, também evitou alterações bioquímicas e histopatológicas induzidas por canamicina, reduziu MDA e grupos SH e restaurou atividade CAT. Conclusão: A administração de doses orais repetidas de D-005 protegeu significativamente contra LRA induzida por canamicina, que pode estar associada aos efeitos antioxidantes e anti-inflamatórios deste extrato.