A5034619264- Malaria Research and Control
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- Hepatitis B Virus Studies
- Toxoplasma gondii Research Studies
- Vibrio bacteria research studies
- Vector-borne infectious diseases
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Research on Leishmaniasis Studies
- Drug Transport and Resistance Mechanisms
- Invertebrate Immune Response Mechanisms
- Immune Cell Function and Interaction
- Vaccine Coverage and Hesitancy
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- COVID-19 epidemiological studies
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Hepatitis Viruses Studies and Epidemiology
- Science and Education Research
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Virology and Viral Diseases
Universidade de São Paulo
2016-2025
Institut Pasteur
2011-2016
Universidade Federal de São Paulo
2006-2013
Background.Plasmodium falciparum and Plasmodium vivax are responsible for most of the global burden malaria. Although accentuated pathogenicity P. occurs because sequestration mature erythrocytic forms in microvasculature, this phenomenon has not yet been noted vivax. The increasing number severe manifestations infections, similar to those observed malaria, suggests that key pathogenic mechanisms (eg, cytoadherence) might be shared by 2 parasites. Methods. Mature vivax–infected erythrocytes...
Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans long-standing malaria vaccine candidate. It considered to have multiple important roles during penetration, primarily structuring interacting rhoptry neck 2 protein transducing force generated parasite motor internalization. Here, we generate Plasmodium sporozoites merozoites...
Surface-associated TRAP (thrombospondin-related anonymous protein) family proteins are conserved across the phylum of apicomplexan parasites. thought to play an integral role in parasite motility and cell invasion by linking extracellular environment with submembrane actomyosin motor. Blood stage forms malaria Plasmodium express a protein called merozoite-TRAP (MTRAP) that has been implicated erythrocyte invasion. Using MTRAP-deficient mutants rodent-infecting P. berghei human-infecting...
Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine chloroquine, but they have limitations, such as poor adherence due frequent oral administration gastrointestinal side effects. To overcome these we developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) the intradermal delivery drugs. In vitro testing showed systems can deliver skin receiver compartment up...
Calcium is a key signalling molecule in apicomplexan parasites and plays an important role diverse processes including gliding motility. Gliding essential for the malaria parasite to migrate from skin liver as well invade host tissues cells. Here we investigated dynamics of intracellular Ca(2+) motility Plasmodium berghei sporozoites by live imaging flow cytometry. We found that cytosolic levels increase when are activated suspension, which sufficient induce secretion integrin-like adhesins...
Malaria, a life-threatening disease caused by Plasmodium parasites, continues to pose significant global health threat, with nearly 250 million infections and over 600 000 deaths reported annually the WHO. Fighting malaria is particularly challenging partly due complex life cycle of parasite. However, technological breakthroughs such as development nucleoside-modified mRNA lipid nanoparticle (mRNA-LNP) vaccine platform, along discovery novel conserved antigens E140 protein, present new...
Salmonella flagellin, the flagellum structural subunit, has received particular interest as a vaccine adjuvant conferring enhanced immunogenity to soluble proteins or peptides, both for activation of antibody and cellular immune responses. In present study, we evaluated enterica FliCd flagellin T cell using model 9-mer (SYVPSAEQI) synthetic H2(d)-restricted CD8(+) cell-specific epitope (CS(280-288)) derived from Plasmodium yoelii circumsporozoite (CS) protein. The effects were determined...
In a recent study, we demonstrated the immunogenic properties of new malaria vaccine polypeptide based on 19 kDa C-terminal fragment merozoite surface protein-1 (MSP1(19)) from Plasmodium vivax and an innate immunity agonist, Salmonella enterica serovar Typhimurium flagellin (FliC). Herein, tested whether same strategy, MSP1(19) component deadly parasite falciparum, could also generate fusion with enhanced immunogenicity. The His(6)FliC-MSP1(19) protein was expressed recombinant Escherichia...
The Apical Membrane Antigen 1 (AMA-1) is considered a promising candidate for development of malaria vaccine against asexual stages Plasmodium. We recently identified domain II (DII) Plasmodium vivax AMA-1 (PvAMA-1) as highly immunogenic region recognised by IgG antibodies present in many individuals during patent infection with P. vivax. study was designed to evaluate the properties bacterial recombinant protein containing PvAMA-1 DII. To accomplish this, administered mice presence each...
Export of most malaria proteins into the erythrocyte cytosol requires Plasmodium translocon exported (PTEX) and a cleavable export element (PEXEL). In contrast, contribution PTEX in liver stages stage is unknown. Here, using FLP/FRT conditional mutatagenesis system, we generate transgenic berghei parasites deficient EXP2, putative pore-forming component PTEX. Our data reveal that EXP2 important for parasite growth critical transition to blood, with impaired their ability patent blood-stage...
Malaria remains an important parasitic disease with a large morbidity and mortality burden. Plasmodium transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts. Recent efforts to develop high-throughput screening (HTS) methods identify that inhibit or kill gametocytes, the sexual stage infectious mosquitoes, have yielded insight into new TB compounds. However, activities of these against gametes, formed in first minutes mosquito infection, typically not...
Plasmodium vivax is the most common species that cause malaria outside of African continent. The development an efficacious vaccine would contribute greatly to control malaria. Recently, using bacterial and adenoviral recombinant proteins based on P. circumsporozoite protein (CSP), we demonstrated possibility eliciting strong antibody-mediated immune responses each three allelic forms CSP (PvCSP). In present study, representing PvCSP alleles (VK210, VK247, vivax-like), as well a hybrid...
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium, affecting more than 200 million people worldwide every year and leading to about half deaths. humans have evolved resistance all current antimalarial drugs, urging for discovery new effective compounds. Given that inhibition deoxyuridine triphosphatase Plasmodium falciparum (PfdUTPase) induces wrong insertions in plasmodial DNA consequently parasite death, this enzyme considered an attractive drug...
Drug resistance is a constant threat to malaria control efforts making it important maintain good pipeline of new drug candidates. Of particular need are compounds that also block transmission by targeting sexual stage parasites. Mature stages relatively resistant all currently used antimalarials except the 8-aminoquinolines not commonly due potential side effects. Here, we synthesized Torin 2 derivative, NCATS-SM3710 with increased aqueous solubility and specificity for Plasmodium...
Transmission of Plasmodium species from a mammalian host to the mosquito vector requires uptake, during an infected blood meal, gametocytes, precursor cells gametes. Relatively little is known about molecular mechanisms involved in developmental switch asexual development sexual differentiation or maturation and survival gametocytes. Here, we show that gene coding for novel putative transporter, NPT1, plays crucial role berghei Parasites lacking NPT1 are severely compromised production...
ABSTRACT A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion vaccine is the first malaria to reach phase III clinical trials. Resistance infection correlated with production of antibodies immunodominant central repeat region CSP. In contrast P. , development against CSP vivax far behind. Based on this gap in our knowledge, we generated a chimeric containing regions fused Salmonella enterica serovar Typhimurium-derived flagellin (FliC) activate innate immune...
The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera, Plasmodium and Toxoplasma, until we genetically engineered viable parasites lacking AMA1. reduction in invasiveness Toxoplasma gondii RH-AMA1 knockout (RH-AMA1(KO)) tachyzoite population, vitro, raised key questions about outcome associated with these tachyzoites once inoculated peritoneal cavity mice. In this study, used AMNIS technology simultaneously quantify...
Malaria is a tropical infectious disease that affects over 219 million people worldwide. Due to the constant emergence of parasitic resistance current antimalarial drugs, discovery new drugs global health priority. Multi-target drug promising and innovative strategy for it currently regarded as one best strategies face resistance. Aiming identify multi-target candidates, we developed an integrative computational approach select multi-kinase inhibitors (MKI) Plasmodium falciparum...