Background Significant progress has been recently achieved in the development of Plasmodium vivax challenge infections humans, which are essential for vaccine and drug testing. With goal accelerating clinical malaria vaccines, outcome experimentally induced naïve semi-immune volunteers by infected mosquito bites was compared. Methods Seven malaria-naïve nine Colombian adults (n = 16) were subjected to 2–4 P. sporozoite-infected Anopheles mosquitoes. Parasitemia levels, manifestations, immune...

Background Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two have been similarly immunized P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety protective efficacy of PvRAS immunization. Methodology/Principal Findings randomized, single-blinded conducted. Duffy positive (Fy+; Pv susceptible) individuals...

Disrupting behaviors linked to movement of primary mosquito vectors, such as diel locomotor activity and visual sensitivity, is a novel plausible malaria control intervention. Diel an output arthropod circadian influenced by factors light, temperature, infection status. The biogenic amines histamine serotonin (5-HT) are ingested with blood differ between healthy hosts those severe malaria. They regulate parasite in Anopheles stephensi , but the degree which aging, interact influence behavior...

Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during infection, which target surface Plasmodium gametocyte/gamete proteins. Some these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte antigen orthologous Pfs48/45, play role parasite fertilization and thus has transmission blocking (TB) activity. Here we describe the expression recombinant protein expressed in Escherichia coli as...

Background Malaria remains endemic in several countries of South America with low to moderate transmission intensity. Regional human migration through underserved areas may be responsible for significant parasite dispersion making the disease resilient interventions. Thus, genetic characterization malarial parasites is an important tool assess how connect via movement infected individuals. Here, four sites geographically separated reporting 80% malaria morbidity Colombia were studied. The...

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from CS formulated Montanide ISA 720. Both antibody- and cell-mediated were analyzed. Antibodies predominantly IgG1 IgG3 isotypes, recognized parasite proteins on immunofluorescent antibody test, partially blocked sporozoite invasion hepatoma cell lines vitro....

Introduction: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality affected patients, consequent untimely child death. In contrast classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation multiple metabolites associated with IEM offering higher sensitivity, low false positive rates high throughput. Aims: Determine concentration levels for amino acids acylcarnitines...

Malaria is strongly predisposed to bacteremia, which associated with increased gastrointestinal permeability and a poor clinical prognosis. We previously identified mast cells (MCs) as mediators of intestinal in malaria described multiple cytokines that rise parasitemia, including interleukin (IL)-10, could protect the host from an inflammatory response alter parasite transmission

Abstract Our previous work demonstrated that basophils regulate a suite of malaria phenotypes, including intestinal mastocytosis and permeability, the immune response to infection, gametocytemia, parasite transmission mosquito Anopheles stephensi. Given activated are primary sources regulatory cytokines IL-4 IL-13, we sought examine contributions these mediators basophil-dependent phenotypes in malaria. We generated mice with depleted for IL-13 (baso IL-4/IL-13 (−)) genotype controls (+)) by...

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate previously assessed in animals and humans. Here, combinations of three synthetic polypeptides corresponding to amino (N), central repeat (R), carboxyl (C) regions the CS formulated Montanide ISA 720 or 51 adjuvants were for immunogenicity rodents primates. BALB/c mice Aotus monkeys divided into test control groups immunized times with doses 50 100 μg placebo. Antigen-specific antimalarial antibodies...

Plasmodium vivax circumsporozoite (PvCS) protein is a major sporozoite surface antigen involved in parasite invasion of hepatocytes and currently being considered as vaccine candidate. PvCS contains dimorphic central repetitive fragment flanked by conserved regions that contain functional domains.We have developed chimeric 137-mer synthetic polypeptide (PvCS-NRC) includes the region I II-plus two natural repeat variants known VK210 VK247. The antigenicity PvCS-NRC was tested using human sera...

Abstract Background Speed congenics is an important tool for creating congenic mice to investigate gene functions, but current SNP genotyping methods speed are expensive. These usually rely on chip or array technologies, and a different assay must be developed each backcross strain combination. “Next generation” high throughput DNA sequencing technologies have the potential decrease cost increase flexibility power of congenics, thus far not been utilized this purpose. Results We took...

Abstract Malaria-induced bacteremia has been shown to result from intestinal mast cell (MC) activation. The appearance of MCs in the ileum and increased permeability enteric bacteria are preceded by an early Th2-biased host immune response infection, characterized IL-4, IL-10, protease (Mcpt)1 Mcpt4, circulating basophils eosinophils. Given functional similarities context allergic inflammation capacity produce large amounts we sought define role permeability, MC influx, development malaria....

Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, total 50 antigens with motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides silico chemically synthesized; circular dichroism studies indicated partial or high content. Antigenicity was evaluated human sera samples from...

Crotalus durissus cumanensis, a rattlesnake endemic to Colombia and Venezuela, is considered one of the most lethal snake species in Latin America. The aim present study was compare protein content biological activity venom obtained from eight specimens C. namely two adults different localities six offspring born captivity. Protein profiles crude venoms were analyzed by SDS-PAGE RP-HPLC, activities evaluated for lethality, edema, defibrination, hemolytic coagulant assess individual pool...

P48/45 is a conserved gametocyte antigen involved in Plasmodium parasite fertilization. A recombinant vivax (Pvs48/45) protein expressed Escherichia coli (E. coli) was highly antigenic and immunogenic experimental animals elicited specific transmission-blocking (TB) antibodies previous pilot study. Here, similar Pvs48/45 gene Chinese Hamster Ovary (CHO) cells we compared its immunoreactivity with the E. product. Specific antibody titers were determined using plasma from Colombian individuals...

An increase in mast cells (MCs) and MCs mediators has been observed malaria-associated bacteremia, however, the role of these granulocytes malarial immunity is poorly understood. Herein, we studied mouse MC protease (Mcpt) 4, an ortholog human chymase, malaria-induced bacteremia using Mcpt4 knockout ( -/- ) mice +/+ C57BL/6J controls, non-lethal parasite Plasmodium yoelii 17XNL. Significantly lower parasitemia was compared with controls by day 10 post infection (PI). Although bacterial 16S...

Malaria strongly predisposes to bacteremia, which is associated with sequestration of parasitized red blood cells and increased gastrointestinal permeability. The mechanisms underlying this disruption are poorly understood. Here, we evaluated the expression factors mast cell activation malaria-associated bacteremia in a rodent model. C57BL/6J mice were infected Plasmodium yoeliiyoelli 17XNL, tissues collected over time assay for circulating levels bacterial 16S DNA, IgE, protease 1 (Mcpt-1)...

We have recently demonstrated that basophils are protective against intestinal permeability during malaria and contribute to reduced parasite transmission mosquitoes. Given IL-18 is an early cytokine/alarmin in has been shown activate basophils, we sought determine the role of basophil IL-18R this phenotype. To address this, infected control [IL18rflox/flox or basoIL-18R (+)] mice with lacking × Basoph8 (-)] Plasmodium yoelii 17XNL, a nonlethal strain mouse malaria. Postinfection (PI),...

Protein α-helical coiled coil structures are known to induce antibodies able block critical functions in different pathogens. In a previous study, total of 50 proteins Plasmodium vivax erythrocytic asexual stages containing structural motifs were identified silico, and the corresponding peptides chemically synthesized. A 43 recognized by naturally acquired plasma samples from both Papua New Guinea (PNG) Colombian adult donors. this association between IgG these clinical immunity was further...

Arthropod-borne viruses or arboviruses, including West Nile virus (WNV), dengue (DENV), and Zika (ZIKV) pose significant threats to public health. It is imperative develop novel methods control these mosquito-borne viral infections. We previously showed that insulin/insulin-like growth factor-1 signaling (IIS)-dependent activation of ERK JAK-STAT has antiviral activity in insects human cells. Continuous immune pressure can lead adaptive mutations during infection. aim elucidate how...