18. Cientistas identificam elementos-chave para vacina da malária
Doença mata pelo menos 1 milhão de pessoas por ano no mundo. Estudo foi apresentado na revista especializada 'PLoS Medicine'
Cientistas identificaram duas moléculas superficiais no parasita da malária que podem permitir o desenvolvimento de uma vacina contra a doença, que mata pelo menos 1 milhão de pessoas por ano no mundo, afirma artigo na revista médica "PLoS Medicine" que circula nesta quarta-feira (20/1).
As moléculas, chamadas antígenos, parecem desencadear uma reação imunológica poderosa em pacientes, ajudando a protegê-los contra a doença em infecções posteriores.
Sob o comando da cientista Freya Fowkes, do Instituto Walter e Eliza Hall de Pesquisas Médicas, de Melbourne (Austrália), os pesquisadores analisaram 33 estudos médicos anteriores que avaliavam pessoas que haviam ficado imunes à malária depois de sofrer a doença.
Eles descobriram que dois antígenos - o MSP-3 e o MSP-119 - provocavam anticorpos particularmente poderosos nos pacientes, o que os protegia em 54% e 18% de novos episódios da doença, respectivamente.
"As pessoas em áreas endêmicas de malária desenvolvem uma imunidade natural", disse Freya à Reuters antes da publicação das conclusões na "PLoS Medicine". "O que (os estudos) fizeram foi ir a essas comunidades e ver a quais antígenos há imunidade e se podemos usar esses antígenos para fazer vacinas." Segundo ela, é possível que haja outros antígenos protetores que ainda não foram estudados.
O parasita da malária se multiplica invadindo os glóbulos vermelhos do sangue. "O parasita usa diferentes antígenos para se acoplar a diferentes moléculas na superfície das células sanguíneas vermelhas (...). Uma vez dentro das células sanguíneas vermelhas, o parasita se divide e se multiplica rapidamente, e a célula sanguínea vermelha estoura e libera ainda mais (parasitas) que contaminam ainda mais células sanguíneas vermelhas", explicou a pesquisadora.
"Pode haver centenas de milhares de células sanguíneas vermelhas infectadas em uma pessoa."
É difícil produzir uma vacina contra a malária porque o parasita é muito diverso, com muitos antígenos em sua superfície. "Com o sarampo, você pega só uma infecção por sarampo e está imune o resto da vida", comparou Freya.
"Com a malária, você precisa de múltiplas infecções para desenvolver uma imunidade de longo prazo à doença. O parasita em si é muito diverso, com muitos diferentes antígenos na superfície (...), e demora um tempo para desenvolver imunidade suficiente a todos os diferentes antígenos (e) para dar uma proteção de longo prazo contra a malária."
(Reuters)
(G1, 19/1)
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The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis
Freya J. I. Fowkes1*, Jack S. Richards1,2, Julie A. Simpson3,James G. Beeson1*
1 Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, 2 Department of Medical Biology, University of Melbourne, Victoria, Australia, 3 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Victoria, Australia
Abstract Top
Background
One of the criteria to objectively prioritize merozoite antigens for malaria vaccine development is the demonstration that naturally acquired antibodies are associated with protection from malaria. However, published evidence of the protective effect of these antibodies is conflicting.
Methods and Findings
We performed a systematic review with meta-analysis of prospective cohort studies examining the association between anti-merozoite immunoglobin (Ig) G responses and incidence of Plasmodium falciparum malaria. Two independent researchers searched six databases and identified 33 studies that met predefined inclusion and quality criteria, including a rigorous definition of symptomatic malaria. We found that only five studies were performed outside sub-Saharan Africa and that there was a deficiency in studies investigating antibodies to leading vaccine candidates merozoite surface protein (MSP)-142 and erythrocyte binding antigen (EBA)-175. Meta-analyses of most-studied antigens were conducted to obtain summary estimates of the association between antibodies and incidence of P. falciparum malaria. The largest effect was observed with IgG to MSP-3 C terminus and MSP-119 (responders versus nonresponders, 54%, 95% confidence interval [CI] [33%–68%] and 18% [4%–30%] relative reduction in risk, respectively) and there was evidence of a dose-response relationship. A tendency towards protective risk ratios (RR<1) was also observed for individual study estimates for apical membrane antigen (AMA)-1 and glutamate-rich protein (GLURP)-R0. Pooled estimates showed limited evidence of a protective effect for antibodies to MSP-1 N-terminal regions or MSP-1-EGF (epidermal growth factor-like modules). There was no significant evidence for the protective effect for MSP-2 (responders versus nonresponders pooled RR, MSP-2FC27 0.82, 95% CI 0.62–1.08, p = 0.16 and MSP-23D7 0.92, 95% CI 0.75–1.13, p = 0.43). Heterogeneity, in terms of clinical and methodological diversity between studies, was an important issue in the meta-analysis of IgG responses to merozoite antigens.
Conclusions
These findings are valuable for advancing vaccine development by providing evidence supporting merozoite antigens as targets of protective immunity in humans, and to help identify antigens that confer protection from malaria. Further prospective cohort studies that include a larger number of lead antigens and populations outside Africa are greatly needed to ensure generalizability of results. The reporting of results needs to be standardized to maximize comparability of studies. We therefore propose a set of guidelines to facilitate the uniform reporting of malaria immuno-epidemiology observational studies.
Please see later in the article for the Editors' Summary
Citation: Fowkes FJI, Richards JS, Simpson JA, Beeson JG (2010) The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis. PLoS Med 7(1): e1000218. doi:10.1371/journal.pmed.1000218
Academic Editor:Philip Andrew Bejon, University of Oxford, United Kingdom
Received: August 4, 2009; Accepted: December 11, 2009; Published: January 19, 2010
Copyright: © 2010 Fowkes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by the National Health and Medical Research Council of Australia (NHMRC,http://www.nhmrc.gov.au) project grant #516756, NHMRC IRIISS grant #361646 and the Victorian State Government Operational Infrastructure Support grant. JGB is supported by a Clinical Career Development Award, and JSR by a Medical Postgraduate Research Scholarship from the NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations:ACD, active case detection; AMA-1, apical membrane antigen-1; BL, block; CI, confidence interval; Ct, C terminus; DNS, data not shown in original manuscript; EBA, erythrocyte binding antigen; EGF, epidermal growth factor-like module; ELISA, enzyme-linked immunosorbent assay; GLURP, glutamate-rich protein; HR, hazard ratio; Ig, immunoglobulin; IRR, incidence rate ratio; ln, natural logarithm; MSP, merozoite surface protein; OR, odds ratio; PCD, passive case detection; reRR, pooled risk ratio using random-effects; RR, risk ratio; VSA, variant surface antigen
* E-mail: fowkes@wehi.edu.au (FJIF); beeson@wehi.edu.au (JGB)
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