Challenges in the research and development of new human vaccines

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2013-11-25T19:29:46Z No. of bitstreams: 1 Barbosa T Challenges in the....pdf: 210220 bytes, checksum: a3500b1dd61d3123c0b596b7594c3fdb (MD5)Made available in DSpace on 2013-11-25T19:29:46Z (GMT). No. of bitstreams: 1 Barbosa T Challenges in the....pdf: 210220 bytes, checksum: a3500b1dd61d3123c0b596b7594c3fdb (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilThe field of vaccinology was born from the observations by the fathers of vaccination, Edward Jenner and Louis Pasteur, that a permanent, positive change in the way our bodies respond to life-threatening infectious diseases can be obtained by specific challenge with the inactivated infectious agent performed in a controlled manner, avoiding the development of clinical disease upon exposure to the virulent pathogen. Many of the vaccines still in use today were developed on an empirical basis, essentially following the paradigm established by Pasteur, ‘‘isolate, inactivate, and inject’’ the disease-causing microorganism, and are capable of eliciting uniform, long-term immune memory responses that constitute the key to their proven efficacy. However, vaccines for pathogens considered as priority targets of public health concern are still lacking. The literature tends to focus more often on vaccine research problems associated with specific pathogens, but it is increasingly clear that there are common bottlenecks in vaccine research, which need to be solved in order to advance the development of the field as a whole. As part of a group of articles, the objective of the present report is to pinpoint these bottlenecks, exploring the literature for common problems and solutions in vaccine research applied to different situations. Our goal is to stimulate brainstorming among specialists of different fields related to vaccine research and development. Here, we briefly summarize the topics we intend to deal with in this discussion

Interferon-gamma production by mononuclear cells in Bacille Calmette-Guérin-revaccinated healthy volunteers predicted long-term antimycobacterial responses in a randomized controlled trial

Study group: Evelin S Oliveiraa,[email protected],Jaqueline S Rodriguesa,[email protected],Elisabete L Conceic¸ ãoa,[email protected],Mauricio R [email protected],Antonio Luis de O A [email protected],Juliana P Bezerra de [email protected],Sergio [email protected], Jamocyr M Marinhoc,[email protected],Manoel Barral-Nettoa,[email protected],Theolis Barbosaa,b,*[email protected] by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-29T12:59:28Z No. of bitstreams: 1 Oliveira ES T interferon gamma....pdf: 814815 bytes, checksum: 75d294d06aab43535db5f6f03a960006 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-29T13:13:07Z (GMT) No. of bitstreams: 1 Oliveira ES T interferon gamma....pdf: 814815 bytes, checksum: 75d294d06aab43535db5f6f03a960006 (MD5)Made available in DSpace on 2017-08-29T13:13:07Z (GMT). No. of bitstreams: 1 Oliveira ES T interferon gamma....pdf: 814815 bytes, checksum: 75d294d06aab43535db5f6f03a960006 (MD5) Previous issue date: 2013Fundação de Amparo à Pesquisa do Estado da Bahia–FAPESB [Convênio 160/03] and Conselho Nacional de Desenvolvimento Científico e Tecnológico [Proc. Nr. 476860/2007-5]. JSR, MP and ELC have received scholarships from FAPESB, and ESO received a scholarship from Coordenação de Aperfeiç oamento de Pessoal de Nível Superior (CAPES).Universidade Federal da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilEscola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Hospital Santa Izabel. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilStudy groupThe Bacille Calmette-Guérin (BCG) vaccine is the only vaccine currently available for tuberculosis, and it demonstrates variable efficacy against the disease. The assessment of new vaccine strategies is hindered by the small annual probability that an infected individual will develop tuberculosis, and the lack of simple and reliable surrogate markers of protection. The frequency of cytokine-producing T cells as well as the production of IFN-γ have been disputed as surrogate markers of protection. We evaluated the evolution of these immune parameters in a population from a high burden city where BCG revaccination has been shown to result in mild protection. We found that individuals whose in vitro IFN-γ responses to mycobacterial antigens had increased by more than 3.3-fold were more likely to maintain higher responses after 1 year and to show increased expansion of IFN-γ-producing T lymphocytes than those with lower or null increase of IFN-γ

Revisiting proteus: do minor changes in lectin structure matter in biological activity? Lessons from and potential biotechnological uses of the Diocleinae subtribe lectins

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-03-24T17:08:26Z No. of bitstreams: 1 Cavada B Revisiting proteus....pdf: 59350 bytes, checksum: 01b4aff56b7c0489edc0e5024ebedea6 (MD5)Made available in DSpace on 2014-03-24T17:08:26Z (GMT). No. of bitstreams: 1 Cavada B Revisiting proteus....pdf: 59350 bytes, checksum: 01b4aff56b7c0489edc0e5024ebedea6 (MD5) Previous issue date: 2001Universidade Federal do Ceará. BioMol – Laboratório. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunoregulação. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunoregulação. Salvador, BA, Brasil.Universidade Federal do Ceará. BioMol – Laboratório. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, Brasil / Universidade Federal do Ceará. Laboratório de Citogenética e Genética Molecular. Departamento de Biologia. Fortaleza, CE, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Imunoregulação. Salvador, BA, Brasil.Significant differences in function have been observed among lectins structurally similar to concanavalin A, but their high homology with this widely used lectin has kept them in obscurity. The observation of large differences in the potency of many of these Diocleinae lectins as stimulators of Interferon-g production by human peripheral blood mononuclear cells has lead to a major effort to unravel their chemical structure and biological activity. Modeling studies of some of these lectins reveal conformational changes in side chains of some residues involved in the carbohydrate-binding site, with possible effects on the ability of these proteins to recognize specific carbohydrate structures. Additionally, all them constitute in fact a mixture of isolectins, which in different proportions could lead to diverse effects. The present review of the biological actions of Diocleinae lectins includes several in vitro and in vivo immunological findings, as well as their effects on insect growth and reproduction. In these systems Diocleinae lectins proved to be quite diverse in their potency. Such diversity in the biological activity of highly related proteins recalls the origin of the name protein: like Proteus, the capability of assuming various forms is the essential feature of this class of molecules

R&D in Vaccines Targeting Neglected Diseases: An Exploratory Case Study Considering Funding for Preventive Tuberculosis Vaccine Development from 2007 to 2014

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-26T18:36:14Z No. of bitstreams: 1 Bessa TC R&D in Vaccines Targeting Neglected Diseases....pdf: 677127 bytes, checksum: 9f3acc3437de7bcc89b39c9f868e1117 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-26T18:46:41Z (GMT) No. of bitstreams: 1 Bessa TC R&D in Vaccines Targeting Neglected Diseases....pdf: 677127 bytes, checksum: 9f3acc3437de7bcc89b39c9f868e1117 (MD5)Made available in DSpace on 2018-02-26T18:46:41Z (GMT). No. of bitstreams: 1 Bessa TC R&D in Vaccines Targeting Neglected Diseases....pdf: 677127 bytes, checksum: 9f3acc3437de7bcc89b39c9f868e1117 (MD5) Previous issue date: 2017National Institute of Science and Technology of Innovation onDiseases of Neglected Populations (INCT-IDPN),Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Bahia. Institute of Collective Health. Salvador, BA, BrazilFederal University of Southern Bahia. Institute of Humanities Arts and Sciences. Itabuna, BA, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilBased on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement

Lectin-induced nitric oxide production

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-10-05T17:40:00Z No. of bitstreams: 1 Andrade JL Lectin-induced nitric ....pdf: 71074 bytes, checksum: f7de8fb9030ae4bcda9517881955be83 (MD5)Made available in DSpace on 2012-10-05T17:40:00Z (GMT). No. of bitstreams: 1 Andrade JL Lectin-induced nitric ....pdf: 71074 bytes, checksum: f7de8fb9030ae4bcda9517881955be83 (MD5) Previous issue date: 1999Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Ceará. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, BrasilUniversidade Federal do Ceará. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, BrasilUniversidade Federal do Ceará. Departamento de Bioquímica e Biologia Molecular. Fortaleza, CE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilConsidering that nitric oxide (NO) may be involved in anti-tumoral and anti-parasite lectin effects, in this report we investigated whether lectin induces NO production. Lectins from Canavalia brasiliensis, Dioclea grandiflora, Pisum arvense (PAA), and concanavalin A induced murine peritoneal cells to produce NO in vitro. PAA induced similar levels to that obtained with lipopolysaccharide plus interferon-gamma. NO production by adherent cells was significantly lower than that of unfractionated cells, suggesting a combination of lectin stimuli directly on macrophages and via lymphocyte stimulation. Ex vivo experiments showed that cells stimulated in vivo could maintain NO production in vitro without further stimuli. NO synthesis blockage in vivo can significantly increase cell numbers in draining lymph nodes after lectin injection compared to unblocked controls, suggesting an in vivo association of lectin stimuli and NO production. Taken together these data show that lectins can induce NO production both in vitro and in vivo

Tuberculosis among Yanomami communities from Alto Rio Negro,State of Amazonas, Brazil, 1990 to 2002

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-23T18:27:32Z No. of bitstreams: 1 Barbosa, T Tuberculosis....pdf: 138680 bytes, checksum: c2ee84b97b349055ee6b169d66c6ee7d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-23T18:53:44Z (GMT) No. of bitstreams: 1 Barbosa, T Tuberculosis....pdf: 138680 bytes, checksum: c2ee84b97b349055ee6b169d66c6ee7d (MD5)Made available in DSpace on 2015-03-23T18:53:44Z (GMT). No. of bitstreams: 1 Barbosa, T Tuberculosis....pdf: 138680 bytes, checksum: c2ee84b97b349055ee6b169d66c6ee7d (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilInstituto Brasileiro para o Desenvolvimento Sanitário. São Gabriel da Cachoeira, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilInstitut Català de la Salut. Unitat de Medicina Tropical i Salut Internacional Drassanes. Barcelona, CatalunyaFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundamentos: Las poblaciones indígenas brasileñas muestran altas tasas de tuberculosis, las cuales pueden ser atribuidas no sólo a las condiciones socio-económicas y a la dificultad de acceso a los servicios de salud, sino también a una posible susceptibilidad intrínseca de estas poblaciones. Buscamos describir los casos y explorar el posible cluster de tuberculosis en familias Yanomami. Método: Estudio descriptivo de casos de tuberculosis en las comunidades Yanomami de Ariabú y Maturacá (São Gabriel da Cachoeira, AM, Brasil) entre 1990 y 2002, basado en informes médicos facilitados por los profesionales de salud trabajando en el área. Las comunidades estudiadas están situadas cerca una de la otra, separadas por un río, pero compartiendo los mismos recursos ambientales, sin diferencias en las condiciones sociales, económicas o de la vivienda. Resultados: En este periodo, fueron registrados 101 casos de tuberculosis, correspondiendo a una incidencia estimada anual de 1.082/100.000 en Ariabú y 2.452/100.000 en Maturacá. Múltiples casos familiares fueron significativamente más frecuentes en la comunidad de Maturacá, independientemente del tamaño familiar, sugiriendo agregación familiar (p<0.001). Conclusiones: La tuberculosis es un serio problema entre los Yanomami. Para mejorar su control en estas comunidades, requerirá de una mejora en las condiciones de las casas, una búsqueda activa y estudio de contactos y mejoras en los medios diagnósticos. Los múltiples casos familiares en los Yanomami deberían ser investigados como un potencial grupo con híper-susceptibilidad para la tuberculosisBackground: Brazilian indigenous populations show high tuberculosis rates, which can be attributable not only to socio-economic conditions and poor access to health care services, but also to an intrinsic susceptibility of these individuals. We describe the distribution of tuberculosis cases in two Yanomami communities, and focus on the occurrence of familial clustering of TB cases. Methods: We have performed a descriptive study of TB cases in the Yanomami communities of Ariabú and Maturacá (São Gabriel da Cachoeira, AM, Brazil) between 1990 and 2002, based on medical records provided by health care professionals working in the area. The communities studied are located close to each other, separated by a river, but sharing the same environmental resources, with no differences in social, economic or housing conditions. Results: In this period, 101 cases of TB were registered, corresponding to an estimated annual incidence after active surveillance of 1,082/100,000 at Ariabú and 2,452/100,000 at Maturacá. Multicase families were significantly more frequent in Maturacá community, independent of family size, suggesting familial aggregation (p<0.001). Conclusions: Tuberculosis is a serious problem among the Yanomami. TB control in Yanomami communities will require improvement in housing conditions, active surveillance, contact tracing and diagnosis. Yanomami multicase families should be investigated as a potential group with hyper-susceptibility to tuberculosis

Correlation between interleukin-10 and in situ necrosis and fibrosis suggests a role for interleukin-10 in the resolution of the granulomatous response of tuberculous pleurisy patients.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-02T19:13:25Z No. of bitstreams: 1 Barbosa T Correlation between....pdf: 384972 bytes, checksum: 27e908da6c9d12feb43c5c98c08f8492 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-03-03T14:18:28Z (GMT) No. of bitstreams: 1 Barbosa T Correlation between....pdf: 384972 bytes, checksum: 27e908da6c9d12feb43c5c98c08f8492 (MD5)Made available in DSpace on 2016-03-03T14:18:28Z (GMT). No. of bitstreams: 1 Barbosa T Correlation between....pdf: 384972 bytes, checksum: 27e908da6c9d12feb43c5c98c08f8492 (MD5) Previous issue date: 2006Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Baiana para o Desenvolvimento das Ciências. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina.. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina.. Salvador, BA, BrasilIn order to identify mediators involved in immune-mediated disease regression, the pleural cytokine and histopathological profile was evaluated in tuberculous pleurisy patients with varied disease duration and clinical presentation, previous to chemotherapy. Interleukin (IL)-10, interferon (IFN)-g and tumor necrosis factor (TNF) levels in pleural fluids were shown to decrease with disease time. IL-10 was positively correlated with IFN-g, TNF and necrosis area in pleural sections. To parallel these findings with disease regression, individuals showing fever, anorexia, and progressive exudate in the pleural cavity (active disease) were compared with patients without symptoms and with a decrease in exudate volume (regressive disease). IFN-g and TNF levels were lower in regressive disease, as well as reduced necrosis area in pleural sections. Our results indicate that tissue destruction and a prominent Th1 response mark the early phase of tuberculous pleurisy and suggest that downmodulation of this response, with the possible participation of IL-10, is associated with disease resolutio

Impact of Bacille Calmette-Guérin revaccination on serum IgE levels in a randomized controlled trial

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-20T16:09:53Z No. of bitstreams: 1 Peleteiro T Impact of Bacille Calmette-Guérin ....pdf: 1175574 bytes, checksum: 2982b238a73d0d4a2965e2c7870786e9 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-20T16:17:43Z (GMT) No. of bitstreams: 1 Peleteiro T Impact of Bacille Calmette-Guérin ....pdf: 1175574 bytes, checksum: 2982b238a73d0d4a2965e2c7870786e9 (MD5)Made available in DSpace on 2018-04-20T16:17:43Z (GMT). No. of bitstreams: 1 Peleteiro T Impact of Bacille Calmette-Guérin ....pdf: 1175574 bytes, checksum: 2982b238a73d0d4a2965e2c7870786e9 (MD5) Previous issue date: 2018Fundação de Amparo à Pesquisa do Estado da Bahia (Programa Primeiros Projetos Nº 160/2003).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Prof. Edgar Santos. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Instituto de Ciências da Saúde. Salvador, BA, Brasil / Rede Brasileira de Pesquisa em Tuberculose, Rio de Janeiro, RJ, BrasilBacille Calmette-Guérin (BCG) downmodulates allergen-specific IgE levels and prevents other atopic responses in experimental models but fails to protect against respiratory allergies. Human responsiveness to BCG is variable and may interfere with protection. Methods: Multivariate models were evaluated to test the possible effect of responsiveness (assessed by IFN-γ production) to BCG revaccination on the modulation of total and allergen-specific serum IgE levels in healthy volunteers participating in a randomized controlled trial. Results: Serum total or Derp-specific IgE levels did not change regardless of the increase in IFN-γ levels. Conclusions: BCG responsiveness does not affect protection against atopy