Developing Countries Can Innovate and Produce Vaccines: The Case of Butantan in Brazil

Since the introduction of vaccines, governments learn that they are the most efficient and inexpensive tool to avoid the spreading of infectious diseases. It resulted in the creation of public research institutes to develop new vaccines, which gave birth to the vaccine industry, that is, growing in size by acquisition of competitors, which estimate that in 2019 they will sell $58 billion, where developing countries represent 80% of the world population, submitted to be dependent of production and prices from large producers. Incapable or not willing to assume the responsibility to produce, accept to purchase vaccines in bulk for filling and labeling as “producers.” Butantan, a public not for profit institute became the first producer of specific anti-venoms and anti-rabies sera. In 1985, Butantan Center of Biotechnology attracted 25 young PhD, which accepted to carry on inovations and technical developments, setting dedicated plants to produce vaccines at affordable cost, aiming self-sufficiency to distribute free through the Ministry of Health. This chapter describes problems and solutions that must be faced to produce vaccine at a cost that developing countries can afford

Mecanismo de ação da insulina

Palestra inaugural dos Seminários de Bioquímica de 1948, pronunciada em 19 de março de 1949. Neste número especial com artigos publicados na Revista de Medicina em 1948, traz um comentário do Prof. Paulo Hilário Nascimento Saldiva (Departamento de Patologia da FMUSP)

Immunization against Pertussis: An Almost Solved Problem or a Headache in Public Health

Whooping cough or pertussis is a serious infectious disease of the human respiratory tract, caused by Gram-negative bacteria Bordetella pertussis and Bordetella parapertussisHU. The current pertussis vaccines may consist of dead cells of B. pertussis (whole cell pertussis vaccines—wPs) or purified antigens from the bacterium (acellular pertussis vaccines—aPs). The aPs are less reactogenic and have been widely used in developed countries for more than two decades, but their high cost of production makes them prohibitive for developing countries, and the accelerated rate of epidemic outbreaks has led to the hypothesis that aPs are less effective than the wP ones. Considering cost-effectiveness, some authors have pointed out questions about the possibility of reintroduction of wP vaccines into the primary doses of pertussis vaccination. The Butantan Institute in São Paulo, Brazil, developed a wP vaccine with low endotoxicity (Plow) obtained by chemical extraction of the lipooligosaccharide (LOS) fraction from the outer membrane of the bacterial cell, showing to be less reactogenic and equally immunogenic and protective as the traditional wP vaccine. The Plow may possibly be introduced into the vaccination schedule for immunization of adolescents and young adults in Brazil, an important epidemiological contribution to reducing the circulation of B. pertussis

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

Generation of a Chinese Hamster Ovary Cell Line Producing Recombinant Human Glucocerebrosidase

Impaired activity of the lysosomal enzyme glucocerebrosidase (GCR) results in the inherited metabolic disorder known as Gaucher disease. Current treatment consists of enzyme replacement therapy by administration of exogenous GCR. Although effective, it is exceptionally expensive, and patients worldwide have a limited access to this medicine. In Brazil, the public healthcare system provides the drug free of charge for all Gaucher's patients, which reaches the order of $ 84million per year. However, the production of GCR by public institutions in Brazil would reduce significantly the therapy costs. Here, we describe a robust protocol for the generation of a cell line producing recombinant human GCR. The protein was expressed in CHO-DXB11 (dhfr(-)) cells after stable transfection and gene amplification with methotrexate. As expected, glycosylated GCR was detected by immunoblotting assay both as cell-associated (similar to 64 and 59 kDa) and secreted (63-69 kDa) form. Analysis of subclones allowed the selection of stable CHO cells producing a secreted functional enzyme, with a calculated productivity of 5.14 pg/cell/day for the highest producer. Although being laborious, traditionalmethods of screening high-producing recombinant cellsmay represent a valuable alternative to generate expensive biopharmaceuticals in countries with limited resources.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)CNPq (Conselho Nacional de Desenvolvimento Cientificoe Tecnologico)CNPQ(Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Fundacao ButantanFundacao Butanta