Vacinas pertussis acelular e pertussis "low": eventos adversos e o papel das mutações

Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.Objetivo: Discutir as recomendações da WHO-OPAS que não consideram indicada a substituição da vacina DTP celular clássica pela DTP acelular e o papel de mutações, em humanos, como principal causa dos raros eventos de convulsões epileptiformes desencadeadas pela vacina pertussis. Revisão dos dados: Os principais componentes relacionados aos efeitos tóxicos da vacina pertussis celular são o lipopolissacarídio da parede celular da bactéria e a toxina pertussis. A remoção de parte da camada lipopolissacarídica permitiu a criação de uma vacina pertussis celular, mais segura e de custo comparável ao da vacina celular tradicional, podendo substituir a vacina pertussis acelular. Conclusão: A nova vacina pertussis, com baixo teor de LPS (Plow) desenvolvida pelo Instituto Butantan, além de oferecer uma vacina mais segura, permite o aproveitamento do lipopolissacarídeo para a produção de monofosforil lipídeo A. Esse componente mostrou-se potente como adjuvante e altamente eficiente quando administrado com a vacina de influenza, levando à possibilidade de se reduzir a dose de antígeno, aumentando a capacidade de produção e redução dos custos

Análise da imunogenicidade e da estabilidade do surfactante pulmonar de origem porcina administrado em coelhos

PURPOSE: To study the immunogenicity and the stability of the porcine pulmonary surfactant preparation produced by the Instituto Butantan. METHOD: Immunogenicity assay: Sixteen New-Zealand-White rabbits (1000 g body weight) were divided into 4 study groups. Each group was assigned to receive either a) Butantan surfactant, b) Survanta® (Abbott Laboratories), c) Curosurf® (Farmalab Chiesi), or d) no surfactant. The surfactants were administered intratracheally, and the animals were collected immediately before and 60 and 180 days after surfactant administration. Sera were assayed for the presence of antisurfactant antibodies by enzyme-linked immunosorbent assay (ELISA). Stability assay: The Butantan surfactant used in this assay had been stored for one year in the refrigerator (4 to 8ºC) and its stability was evaluated in distinct assay conditions using a premature rabbit model. RESULTS: Immunogenicity assay: None of the surfactants analyzed triggered antibody immune responses against their components in any of the animals. Stability assay: The results of this study demonstrate that Butantan surfactant was as effective as Curosurf when both were submitted to the adverse circumstance of short- and long-term storage at room temperature. A similar level of efficacy for the Butantan surfactant, as compared to Curosurf was demonstrated by the pulmonary dynamic compliance, ventilatory pressure, and pressure-volume curve results. CONCLUSION: The results of our study demonstrate that Butantan surfactant may be a suitable alternative for surfactant replacement therapy.OBJETIVO: Estudar a imunogenicidade e a estabilidade do surfactante de origem porcina produzido pelo Instituto Butantan. MÉTODO: Experimento imunogenicidade: 16 coelhos da raça New-Zealand-White (Peso de 1000g) foram divididos em grupos de 4 animais. Cada grupo foi designado para receber: a) Surfactante do Butantan, b) Survanta® (Abbott Laboratories), c) Curosurf (Farmalab Chiesi) e d) nenhum tratamento com surfactante. Os surfactantes foram administrados via intratraqueal e o sangue dos animais foi coletado antes, 60 e 180 dias após a administração do surfactante. O soro obtido foi analisado quanto a presença de anticorpos anti-surfactante pelo método ELISA (enzyme-linked immunosorbent assay). Experimento estabilidade: O surfactante do Butantan usado neste experimento tinha sido armazenado por um ano em refrigerador (4 a 8°C) e sua estabilidade foi analisada em condições distintas de experimentação, usando o modelo de coelho prematuro. RESULTADOS: Experimento imunogenicidade: Nenhum dos surfactantes analisados determinou a produção de anticorpos contra seus constituintes. Experimento estabilidade: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan mostrou eficácia semelhante a do Curosurf após ter sido submetido à condições adversas ao longo do tempo. A eficácia foi demonstrada através da complacência pulmonar dinâmica, pressão ventilatória e da curva pressão-volume. CONCLUSÃO: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan pode representar um tratamento alternativo de reposição de surfactante

L'effet des métaux lourds sur l'organisation supérieure de la chromatine, les phénotypes nucléaires et la survie de Triatoma infestans Klug (Hemiptera, Reduviidae)

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOThe nuclear phenotypes and survival of the hemipteran, Triatoma infestans (Hemiptera, Reduviidae), were studied in specimens treated with copper sulfate and methylmercury. The objective was to determine whether changes in chromatin supraorganization and insect survival similar to those promoted by other stressing agents could also be induced by heavy metals. At the concentrations used, copper sulfate and methylmercury were toxic to the cells, mainly inducing nuclear degeneration in the Malpighian tubules and being lethal to a large part of the insect population. Although some individual resistance was found, especially in fasted specimens, heavy metals were found to be much more lethal than was, for instance, a thermal shock at 0 °C for 12 h. The nuclear phenotypes detected after heavy metal treatment were similar to those reported under other stressing conditions. However, the frequency at which nuclei exhibited aspects of heterochromatin unraveling was much higher than that found in fasted and thermal‐shocked specimens, and was independent of the heavy metal type used. If this phenotype represents an attempt to improve opportunities for extensive cell and insect survival, it was not sufficiently effective. In 5th instar nymphs, the effect of CuSO4 on chromatin supraorganization was detected at early steps of spermatogenesis but not in the cells which were at late spermiogenesis when the metal was administered. This is probably due to changes in nuclear protein composition and to the tightly packed state of the DNA‐ protein complexes occurring at spermiogenesis, which may protect chromatin from damages. However, when CuSO4 was supplied to 4th instar nymphs, it slowed down the spermiogenesis process, possibly due to several factors including Cu2+ binding to DNA phosphates743209218CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãoLes phénotypes nucléaires et la survie de l'hémiptère Triatoma infestans ont été étudiés sur des spécimens traités avec du sulfate de cuivre et du méthyle de mercure. L'objectif a été de déterminer si les changements provoqués par d'autres agents stressants sur l'organisation supérieure de la chromatine et la survie de l'insecte peuvent être induit aussi par les métaux lourds. Il est apparu qu'aux concentrations utilisées, le sulfate de cuivre et le méthyle de mercure sont toxiques pour les cellules, provoquent principalement une dégénération nucléaire dans des organes tels que les tubes de Malpighi, et sont léthaux pour une grande partie de la population. Bien qu'une certaine résistance individuelle ait été trouvée particulièrement chez les spécimens à jeun, les métaux lourds se sont révélés beaucoup plus léthaux que, par example, un choc thermique de 12 h à 0 °C. Les phénotypes nucléaires observés après traitement aux métaux lourds sont similaires à ceux décrits dans d'autres conditions stressantes. Toutefois, la fréquence avec laquelle les noyaux ont montré des aspects déroulés de l'hétérochromatine a été beaucoup élevée que chez les spécimens soumis au jeun ou à un choc thermique, quelque soit le métal utilisée. Si ce phénotype correspond à une tentative d'amélioration de la survie de la cellule et de l'insecte, cela n'est pas suffisant. Chez les nymphes au 5e. étage, l'effet du sulfate de cuivre sur l'organisation supérieure de la chromatine a été observé dès les premières étages de la spermatogenèse, mais pas sur les cellules qui se trouvaient en spermiogenèse avancée lorsque le métal fut fourni. Cela est probablement dû à des changements dans la composition protéinique du noyaux et à la structure dense des complexes ADN‐protéines lors de la spermiogenèse, qui protégerait la chromatine. Toutefois, ce même métal, fourni à des nymphes au 4e étage, relentit la spermiogenèse, probablement à cause de facteurs diverses, inclusivement son attachement avec les phosphates de l'AD

Vacinas pertussis acelular e pertussis low: eventos adversos e o papel das mutações

Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.Objetivo: Discutir as recomendações da WHO-OPAS que não consideram indicada a substituição da vacina DTP celular clássica pela DTP acelular e o papel de mutações, em humanos, como principal causa dos raros eventos de convulsões epileptiformes desencadeadas pela vacina pertussis. Revisão dos dados: Os principais componentes relacionados aos efeitos tóxicos da vacina pertussis celular são o lipopolissacarídio da parede celular da bactéria e a toxina pertussis. A remoção de parte da camada lipopolissacarídica permitiu a criação de uma vacina pertussis celular, mais segura e de custo comparável ao da vacina celular tradicional, podendo substituir a vacina pertussis acelular. Conclusão: A nova vacina pertussis, com baixo teor de LPS (Plow) desenvolvida pelo Instituto Butantan, além de oferecer uma vacina mais segura, permite o aproveitamento do lipopolissacarídeo para a produção de monofosforil lipídeo A. Esse componente mostrou-se potente como adjuvante e altamente eficiente quando administrado com a vacina de influenza, levando à possibilidade de se reduzir a dose de antígeno, aumentando a capacidade de produção e redução dos custos.13113

Analysis of the immunogenicity and stability of a porcine pulmonary surfactant preparation administered in rabbits

PURPOSE: To study the immunogenicity and the stability of the porcine pulmonary surfactant preparation produced by the Instituto Butantan. METHOD: Immunogenicity assay: Sixteen New-Zealand-White rabbits (1000 g body weight) were divided into 4 study groups. Each group was assigned to receive either a) Butantan surfactant, b) Survanta® (Abbott Laboratories), c) Curosurf® (Farmalab Chiesi), or d) no surfactant. The surfactants were administered intratracheally, and the animals were collected immediately before and 60 and 180 days after surfactant administration. Sera were assayed for the presence of antisurfactant antibodies by enzyme-linked immunosorbent assay (ELISA). Stability assay: The Butantan surfactant used in this assay had been stored for one year in the refrigerator (4 to 8ºC) and its stability was evaluated in distinct assay conditions using a premature rabbit model. RESULTS: Immunogenicity assay: None of the surfactants analyzed triggered antibody immune responses against their components in any of the animals. Stability assay: The results of this study demonstrate that Butantan surfactant was as effective as Curosurf when both were submitted to the adverse circumstance of short- and long-term storage at room temperature. A similar level of efficacy for the Butantan surfactant, as compared to Curosurf was demonstrated by the pulmonary dynamic compliance, ventilatory pressure, and pressure-volume curve results. CONCLUSION: The results of our study demonstrate that Butantan surfactant may be a suitable alternative for surfactant replacement therapy

Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model.

While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control-rats received saline; Adjuvant-rats received the adjuvant MPLA, and Vaccine-rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy

Reproductive outcome from rats treated with saline (Control), MPLA (Adjuvant) or MPLA + recombinant peroxidoxin of <i>Leishmania braziliensis</i> (Vaccine) during pregnancy.

<p>Reproductive outcome from rats treated with saline (Control), MPLA (Adjuvant) or MPLA + recombinant peroxidoxin of <i>Leishmania braziliensis</i> (Vaccine) during pregnancy.</p

Ossification sites of rats treated with saline (Control), MPLA (Adjuvant) or MPLA + recombinant peroxidoxin of <i>Leishmania braziliensis</i> (Vaccine) during pregnancy.

<p>Ossification sites of rats treated with saline (Control), MPLA (Adjuvant) or MPLA + recombinant peroxidoxin of <i>Leishmania braziliensis</i> (Vaccine) during pregnancy.</p