Global genetic diversity of the Plasmodium vivax transmission-blocking vaccine candidate Pvs48/45.

Background: Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity, suggesting its potential as a P. vivax transmission-blocking vaccine candidate.

Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for malaria diagnosis in P. vivax endemic settings of Colombia.

Background: Most commonly used malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections which are frequent in low transmission settings. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too laborious for field deployment. In this study, the applicability of a malaria diagnosis kit based on loop-mediated isothermal amplification (mLAMP) was assessed in malaria endemic areas of Colombia with Plasmodium vivax predominance.

Plasmodium vivax sporozoite challenge in malaria-naïve and semi-immune Colombian volunteers.

Background: Significant progress has been recently achieved in the development of Plasmodium vivax challenge infections in humans, which are essential for vaccine and drug testing. With the goal of accelerating clinical development of malaria vaccines, the outcome of infections experimentally induced in naïve and semi-immune volunteers by infected mosquito bites was compared.

Methods: Seven malaria-naïve and nine semi-immune Colombian adults (n = 16) were subjected to the bites of 2-4 P.

Computational prediction and experimental assessment of secreted/surface proteins from Mycobacterium tuberculosis H37Rv.

The mycobacterial cell envelope has been implicated in the pathogenicity of tuberculosis and therefore has been a prime target for the identification and characterization of surface proteins with potential application in drug and vaccine development. In this study, the genome of Mycobacterium tuberculosis H37Rv was screened using Machine Learning tools that included feature-based predictors, general localizers and transmembrane topology predictors to identify proteins that are potentially secreted to the surface of M. tuberculosis, or to the extracellular milieu through different secretory pathways.

Atomic fidelity of subunit-based chemically-synthesized antimalarial vaccine components.

The tri-dimensional (3D) structure determined by NMR of functionally relevant High Activity Binding Peptides (HABPs) of chemically-synthesized malarial proteins, involved in invasion to target cells, is practically identical, at the atomic level, to their corresponding recombinantly produced proteins, determined by X-ray crystallography. Both recombinant proteins as well as these chemically-synthesized HABPs bind to host-cell receptors through channels or troughs formation, stabilized by hydrogen bonding; most of them are located on distant segments to the highly polymorphic, highly antigenic, strain specific amino acid sequences the parasite uses to evade immune pressure. When these immunologically silent conserved HABPs are specifically modified, they become highly immunogenic and capable of inducing protective immune responses, supporting the specifically modified minimal subunit-based, multiepitopic, chemically-synthesized vaccines concept.

Synthetic peptides from conserved regions of the Plasmodium falciparum early transcribed membrane and ring exported proteins bind specifically to red blood cell proteins.

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) 10.2 and 4, to identify specific RBC binding regions in these proteins.

Structural characteristics of immunogenic liver-stage antigens derived from P. falciparum malarial proteins.

A fully effective antimalarial vaccine must contain multiple proteins from the different development stages of Plasmodium falciparum parasites involved in host-cell invasion or their biologically active fragments. It must therefore include sporozoite molecules able to induce protective immunity by blocking the parasite's access to hepatic cells, and/or proteins involved in the development of this stage, amongst which are included the Liver Stage Antigen-1 (LSA-1) and the Sporozoite and Liver Stage Antigen (SALSA). Our studies have focused on the search for an association between the structure of high activity binding peptides (HABPs), including both conserved native and their modified analogues, and their ability to bind to the MHC Class II HLA-DR molecules during formation of the MHCII-peptide-TCR complex leading to inducing the appropriate immune response.