A coqueluche é uma doença contagiosa, causada por Bordetella pertussis e B. parapertussis e as vacinas de células inteiras (WCPs) contra pertussis, embora eficazes, foram associadas a efeitos indesejáveis. Já as vacinas pertussis acelulares são menos reatogênicas, mas caras, o que as torna inviáveis para países em desenvolvimento. Nesse estudo, avaliamos a resposta imune induzida por uma vacina pertussis celular com menor teor de LOS (Plow), desenvolvida pelo Instituto Butantan. Para isso, camundongos C57BL-6 foram imunizados com WCP tradicional ou Plow, formulada com MPL-A de B. pertussis ou com Hidróxido de Alumínio e vacinas tríplice bacterianas com componente pertussis acelular, Pertacel ou Adacel. Após o esquema de imunização, foi avaliada a resposta imune humoral e celular contra a B. pertussis, e B. parapertussis, além de resposta inata a um antígeno não relacionado, BCG. Ensaio de transmissão também foi realizado, após desafio com B. pertussis ou B. parapertussis. Nossos resultados consolidam a avaliação da resposta imune humoral e celular induzida pela Plow, além de apresentar resultados bastante interessantes relativos à atividade da Plow na diminuição da transmissão bacteriana, tanto de pertussis quanto de parapertussis. / Bordetella pertussis and B. parapertussis are the causative agents of whooping cough. Whole cell pertussis (wPs) vaccines, although effective, were associated with undesirable effects. On the other hand, aP vaccines are less reactogenic, but expensive, which made their use unable for developing countries. In this study, we assessed the immunological response, induced by a whole cell pertussis vaccine with low LOS content (Plow), developed by Instituto Butantan. To this, C57BL-6 mice were immunized with traditional whole cell pertussis vaccine or Plow, administrated with Monophosporil lipid A from B.pertussis or Aluminum hydroxide, and diphtheria-tetanus-acellular pertussis vaccines, Pertacel or Adacel. After the immunization scheme, were evaluated humoral and cellular immune responses against B. pertussis and B. parapertussis, in addition to innate response to an unrelated antigen, BCG. Transmission assay was also performed, after B. pertussis or B. parapertussis challenge. Our results consolidated the immune humoral and cellular responses induced by Plow, besides interesting results with regards the efficacy of the vaccine in decreasing the transmission of B. pertussis and B. parapertussis in mice.

Area-wide vaccination against pertussis, also known as whooping cough, has been going on since the 40th - 50th of the last century. In our country this vaccination started in 1958. The World Health Organization estimates that worldwide 20 to 30 million people per year contract pertussis. Patients from developing countries account for 90% of cases. Pertussis is the cause of the death of around 200 000 - 300 000 people per year, up to 85% of whom are children under 2 years of age. As the only source of the bacteria Bordetella pertussis are humans, they are also suitable candidate for the elimination. Therefore, the WHO established an ambitious plan to reduce the incidence of pertussis below 0.1 per 100 000 inhabitants by the year 2000. However, no country succeeded in meeting this plan´s objectives on a long-term basis and since the 80th of the 20th century there has been an increasing trend of the disease incidence across all age groups worldwide. As the proof of severity of this issue pertussis was categorized among the so-called "emerging infectious diseases", that is re-emerging diseases. Diseases whose incidence has increased in recent decades and which could become a major health problem in the near future are classified into this category. In the case of pertussis, the most effective prevention is high vaccination rates in the population, especially children. The theoretical part of the thesis summarizes the current knowledge about pertussis. In the practical part I focused on the incidence and development of the disease in the South Bohemian Region in the years 2005 - 2010, with regard to individual age groups. The results show that in the South Bohemian Region the incidence was rising. The highest incidence was in the age group of 10 to 14 years. Another purpose of the research was to compare the incidence of pertussis in the South Bohemian Region with other regions of the CR. The South Bohemian region in the surveyed 6-year-period ranked among the regions with the highest incidence.

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<p>Despite the advanced knowledge of the mechanisms of influenza infection and improved vaccines, Influenza A Virus still causes a life-threatening respiratory disease, especially during pandemics. Past investigations have proposed a synergism between Influenza A virus and a simultaneous or subsequent bacterial superinfection as the predominant cause of death. The recent development of animal models to study these heterologous infections has shed light onto the diverse mechanisms by which Influenza A Virus may increase the susceptibility to contract a secondary bacterial infection. These studies suggested an important role for the innate immune system in mediating such disease. We developed a model of heterologous infection combining Influenza A Virus and <em>Bordetella parapertussis</em> that demonstrated a critical role for MIP-2 to drive pulmonary neutrophilia in the pathology associated with bacterial superinfection of influenza. However, the origin of this increased MIP-2 production and the mechanisms underlying the immunopathology remained to be elucidated. The present studies proposed IL-1β overproduction as the upstream cause of the increased MIP-2 production observed in heterologous infection. This exaggerated IL-1β production was likely related to the increased bacterial burden observed in heterologously infected mice. This study also demonstrated that reduction in IL-1β production by blockade of the inflammasome seemed to provide an improvement in the clinical symptoms and the immunopathology of the disease. Thus, interventions to attenuate the exacerbated bacterial burden and the inflammatory responses derived from the subsequent IL-1β overproduction should be further investigate as possible therapeutic approaches to treat bacterial superinfections.</p> / Master of Science (MSc)