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      Vacinas em desenvolvimento: estreptococo do grupo B, herpes-zóster, HIV, malária e dengue Translated title: Vaccines under development: group B streptococcus, herpes-zoster, HIV, malaria and dengue

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          Abstract

          OBJETIVOS: As vacinas contra o estreptococo B, o herpes-zóster, o HIV, a malária e a dengue, selecionadas por critérios de comercialização iminente ou devido a problemas específicos para sua obtenção, foram objeto de uma revisão sobre o estado atual do seu desenvolvimento. FONTE DOS DADOS:Foi realizada revisão da literatura através da MEDLINE no período de 1996 a 2006, sobre a epidemiologia e imunologia das doenças, analisando tanto os maiores problemas para a obtenção de uma vacina como o estado atual dos estudos, com ênfase para os que estavam em fase mais adiantada. SÍNTESE DOS DADOS: Cada uma das cinco doenças escolhidas apresenta problemas específicos para o desenvolvimento de uma vacina. No entanto, a maioria deles já foi ou está em vias de ser resolvido, permitindo prever que uma vacina - ou vacinas - eficaz e segura estará disponível em futuro próximo. CONCLUSÕES:Apesar dos problemas enfrentados para o desenvolvimento dessas vacinas, os avanços da biologia molecular e da imunologia permitiram superar a maioria deles, abrindo a perspectiva para a obtenção de novas vacinas.

          Translated abstract

          OBJECTIVES: To review the current state of development of streptococcus B, herpes-zoster, HIV, malaria and dengue vaccines. These vaccines were selected both because of imminent commercial release and because of specific problems with their development. SOURCES OF DATA: A review of the literature was performed by means of a MEDLINE search, on the period 1996 to 2006, for the epidemiology and immunology of these diseases, analyzing both the greatest obstacles to creating a vaccine and the current state of research, with emphasis on studies in the most advanced stages. SUMMARY OF THE FINDINGS: Each of the five diseases chosen presents specific problems for vaccine development. Nevertheless, in the majority of cases these have been or are in sight of being resolved, allowing for the prediction that a safe and effective vaccine - or vaccines - will be available in the near future. CONCLUSIONS: Despite the problems faced in developing these vaccines, advances in molecular biology and immunology have made it possible to overcome most obstacles, opening up the prospects for new vaccines.

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          Dengue: defining protective versus pathologic immunity.

          Dengue is an expanding public health problem, and an effective vaccine remains elusive. This review discusses how the significant influence of sequential infection with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine-induced immune responses.
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            Understanding dengue pathogenesis: implications for vaccine design

            In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50 -100 million cases of acute febrile disease every year, including more than 500 000 reported cases of the severe forms of the disease - dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease.
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              Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research.

              The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory anti-parasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                jped
                Jornal de Pediatria
                J. Pediatr. (Rio J.)
                Sociedade Brasileira de Pediatria (Porto Alegre )
                1678-4782
                July 2006
                : 82
                : 3 suppl
                : s115-s124
                Affiliations
                [1 ] Universidade Estadual de Campinas Brazil
                [2 ] Instituto de Infectologia Emilio Ribas
                [3 ] Hospital e Maternidade Santa Joana
                [4 ] Universität Freiburg Deutschland
                Article
                S0021-75572006000400014
                10.1590/S0021-75572006000400014
                fc477121-369d-48a7-ba9e-76f6ad1c8081

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0021-7557&lng=en
                Categories
                PEDIATRICS

                Pediatrics
                Streptococcus B,herpes-zoster,malaria,dengue,AIDS,HIV,vaccine,Estreptococo B,herpes-zóster,malária,vacina
                Pediatrics
                Streptococcus B, herpes-zoster, malaria, dengue, AIDS, HIV, vaccine, Estreptococo B, herpes-zóster, malária, vacina

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