RESUMO
Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.
Assuntos
Antígenos de Protozoários/genética , Genes de Protozoários/genética , Malária Falciparum/fisiopatologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/sangue , Sequência de Bases , Criança , Clonagem Molecular , Primers do DNA , Membrana Eritrocítica/parasitologia , Regulação da Expressão Gênica/genética , Humanos , Malária Falciparum/sangue , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transcrição Gênica/genéticaRESUMO
The influenza A/H1N1 pandemic in 2009 taught us that the monitoring of vaccine benefits and risks in Europe had potential for improvement if different public and private stakeholders would collaborate better (public health institutes (PHIs), regulatory authorities, research institutes, vaccine manufacturers). The Innovative Medicines Initiative (IMI) subsequently issued a competitive call to establish a public-private partnership to build and test a novel system for monitoring vaccine benefits and risks in Europe. The ADVANCE project (Accelerated Development of Vaccine benefit-risk Collaboration in Europe) was created as a result. The objective of this paper is to describe the perspectives of key stakeholder groups of the ADVANCE consortium for vaccine benefit-risk monitoring and their views on how to build a European system addressing the needs and challenges of such monitoring. These perspectives and needs were assessed at the start of the ADVANCE project by the European Medicines Agency together with representatives of the main stakeholders in the field of vaccines within and outside the ADVANCE consortium (i.e. research institutes, public health institutes, medicines regulatory authorities, vaccine manufacturers, patient associations). Although all stakeholder representatives stated they conduct vaccine benefit-risk monitoring according to their own remit, needs and obligations, they are faced with similar challenges and needs for improved collaboration. A robust, rapid system yielding high-quality information on the benefits and risks of vaccines would therefore support their decision making. ADVANCE has developed such a system and has tested its performance in a series of proof of concept (POC) studies. The system, how it was used and the results from the POC studies are described in the papers in this supplementary issue.