Generation of human monoclonal antibodies against the infective forms of Plasmodium vivax

Abstract

Monoclonal antibodies have emerged as important candidates for the treatment and prevention of various diseases, including cancer, autoimmune diseases and, more recently, infectious diseases. Malaria remains the deadliest vector-borne infection globally and is caused by the inoculation of Plasmodium spp sporozoites during the bite of an infected mosquito. Despite being responsible for over 70% of malaria cases in Brazil, there is no available vaccine against Plasmodium vivax (Pv). Solutions for prevention/treatment of infection by this species are extremely relevant, especially in the context of the Brazilian reality. Previous studies have demonstrated the effectiveness of a single dose of human monoclonal antibodies (hmAb) targeting the Plasmodium falciparum (Pf) circumsporozoite protein (CSP), the major surface protein of sporozoites, in completely blocking Pf sporozoite infection. Thus, the primary objective of this project is to produce and characterize hmAbs against Pv. This involves cloning and expressing DNA sequences that encode the variable portion of the B cell receptor specific for the CSP protein obtained from blood samples from donors previously infected with malaria. To achieve these goals, we propose an internship at The Rockefeller University, under the supervision of Dr. Michel Nussenzweig, who possesses extensive experience in this methodology and has made significant contributions in this field. The ultimate goal of this proposal is to produce and characterize hmAbs with neutralizing capacity against Pv sporozoites, contributing to the advancement of malaria research and therapeutic strategies.