Targeting Plasmodium vivax MSP1-19 protein to two distinct dendritic cells subpopulations using prime-boost strategies

Abstract

Malaria is a serious global public health problem and has become a research priority in vaccine development. Despite continued efforts, there is still no fully effective vaccine against the disease. Several vaccine strategies have been developed using different parasite preparations that induce only partial protection against the infection. In recent years, antigen targeting to dendritic cells (DCs) via monoclonal antibodies (mAbs) fused to proteins of interest (chimeric mAbs) has become a very efficient vaccine tool for inducing adaptive responses against pathogens. Thus, the present work aims to evaluate the induction of immune response in animals immunized with combinations of anti-DEC205 and anti-DCIR2 mAbs. For this purpose, we will use combinations of the anti-DEC205 and anti-DCIR2 chimeric mAbs fused to the Plasmodium vivax protein MSP1-19 protein coupled with the PADRE (Pan-allelic DR epitope) epitope. The use of the PADRE epitope-conjugated with MSP1-19 fragment in immunization protocols will allow the monitoring of the cellular immune response directed against PADRE and the humoral immune response directed against MSP1-19. A challenge will be performed with a P. berghei (murine parasite) transgenic strain expressing P. vivax MSP1-19 in order to evaluate the protection of different groups of immunized animals. Results obtained from the analysis of the induction of immune responses and from the protection mediated by anti-MSP1-19 antibodies may help in the development of more effective malaria vaccines and contribute to lower mortality and morbidity rates, especially in endemic areas. (AU)