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The N-terminal domain of the circumsporozoite protein (CSP) has been largely neglected in the search for a malaria vaccine in spite of being a target of inhibitory antibodies and protective T cell responses in mice. Thus, in order to develop this region as a vaccine candidate to be eventually associated with other candidates and, in particular, with the very advanced C-terminal counterpart, synthetic...
The development of a safe and effective malaria vaccine is impeded by the complexity of the Plasmodium life cycle. A vaccine that elicits both cell-mediated and humoral immune responses might be needed for protection against this multistage parasitic infection. Apical membrane antigen 1 (AMA-1) plays a key role in erythrocytic invasion but is also expressed in sporozoites and in late stage liver schizonts,...
Detergent-resistant lipid raft membrane-associated Pf12, Pf38 and Pf41 proteins belong to the Cys 6 family, whose members are implicated in Plasmodium falciparum invasion to erythrocytes. We have analyzed the interaction between 20-mer-long synthetic peptides spanning the entire Pf12, Pf38 and Pf41 sequences and erythrocytes. Eight high-activity binding peptides (HABPs) were identified in...
Gram positive food-grade bacteria such as lactococci have significant advantages over attenuated pathogens as vaccine delivery vehicles because of their inherently greater safety. Plasmodium falciparum merozoite surface antigen 2 (MSA2) was expressed in recombinant Lactococcus lactis both intracellularly and covalently anchored to the peptidoglycan of the cell wall (MSA2cP). Balb/c mice of different...
Severe malaria pathology is directly associated with cytoadherence of infected red blood cells (iRBCs) to healthy RBCs and/or endothelial cells occurring during the intraerythrocytic development of Plasmodium falciparum. We synthesized, as 20-mer long peptides, the members of the ring exported (REX) protein family encoded in chromosome 9, as well as the early transcribed membrane proteins (E-TRAMP)...
Antibodies play a key role in controlling blood stage malaria infections, and an effective blood stage malaria vaccine will likely require that it induce vaccine-specific memory B cells (MBCs). Our previous studies showed that the addition of the TLR9 agonist CpG to Plasmodium falciparum protein subunit vaccines greatly increased their efficacy in inducing MBCs in nonimmune U.S. volunteers. Here we...
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