Keywords: Human monoclonal antibodies, Plasmodium falciparum, malaria, PfEMP1, PfMSP1, pregnancy-associated malaria, severe childhood malaria, acquired immunity
The overall objective is to generate human monoclonal antibodies (HumAbs) with specificity for Plasmodium falciparum antigens of importance in acquired protection to P. falciparum-induced malaria. The specific objectives are: (i) to generate HumAbs with specificity for antigens exposed on the surface of infected erythrocytes, (ii) to generate HumAbs with specificity for variants of the PfMSP1 antigen and (iii) to test the reactivity and specificity of the developed HumAbs with respect to P. falciparum isolates obtained from infected individuals.
An innovative technology developed by a member of the consortium allows for the efficient generation and production of HumAbs. It will be applied in order to generate antibodies with specificity for PfMSP1 and PfEMP1. Both these antigens are strongly implicated in protective immunity to P. falciparum infection, based on recent research data. The project goes clearly beyond the current state-of-the-art in malaria research by combining groundbreaking technology with rational, evidence-based selection of candidate parasite antigens as targets of therapeutic and prophylactic intervention. The approach holds the promise of overcoming existing obstacles to achieve efficient intervention against malaria.
The main antigenic targets of the protective immunity to P. falciparum infection, as developed by people living in areas of stable parasite transmission, are expressed on the intact surface of infected erythrocytes or free merozoite stage parasites, and are encoded either by polymorphic single-copy genes or by clonally variant multi-gene families. This has greatly obstructed traditional approaches towards the development of effective vaccines as new prophylactic interventions against malaria.
To develop panels of human monoclonal IgG antibodies with specificity for a representative polymorphic single-copy antigen (PfMSP1) and for specific members of the PfEMP1 antigens encoded by the clonally variant var multigene family.
“Proof-of-principle” data by developing HumAbs with specificity for a representative polymorphic single-copy antigen (PfMSP1) and for specific members of the PfEMP1 antigens encoded by the clonally variant var multigene family.
Malaria vaccine research tools and passive therapeutic immunization.
Department of Infectious Diseases M7641
Copenhagen University Hospital (Rigshospitalet)
Blegdamsvej 9, 2100 Copenhagen Ø
Tel.: +45 35 45 79 57
Fax: +45 35 45 76 44
E-mail : email@example.com
|Official Address||Other Information|
|2||Antonio Lanzavecchia||Institute for Biomedical Research
Via Vincenzo Vela 6
|Tel.: +41 91 8200310
Fax: +41 91 8200312
|3||Anthony Holder||Division of Parasitology
The National Institute for Medical Research
London NW7 1AA
|Tel.: +44 208 959 3666/ 2175 |
Fax: +44 208 913 8593
|4||John Lusingu||Department of Epidemiology and Clinical Trials
National Institute for Medical