A5009708727- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Malaria Research and Control
- Insect symbiosis and bacterial influences
- Insect Resistance and Genetics
- Neurobiology and Insect Physiology Research
- Insect Pest Control Strategies
- Viral Infections and Vectors
- Vector-borne infectious diseases
- vaccines and immunoinformatics approaches
- Computational Drug Discovery Methods
- Insect Utilization and Effects
- Insect and Pesticide Research
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Veterinary Pharmacology and Anesthesia
- Thermoregulation and physiological responses
- Hepatitis B Virus Studies
- CRISPR and Genetic Engineering
- Vector-Borne Animal Diseases
- Genetics, Bioinformatics, and Biomedical Research
- Thermal Regulation in Medicine
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- Biological Research and Disease Studies
Walter Reed Army Institute of Research
2015-2021
National Institute of Allergy and Infectious Diseases
2013-2014
National Institutes of Health
2010-2014
Johns Hopkins University
2006-2012
Kettering University
2006
Leiden University
2006
Biotechnology Institute
2006
University of Maryland, College Park
2006
Hemocytes synthesize key components of the mosquito complement-like system, but their role in activation antiplasmodial responses has not been established. The effect activating Toll signaling hemocytes on Plasmodium survival was investigated by transferring or cell-free hemolymph from donor mosquitoes which suppressor cactus silenced. These transfers greatly enhanced immunity, indicating that are active players through an effector/effectors regulated pathway. A comparative analysis hemocyte...
Translational repression of messenger RNAs (mRNAs) plays an important role in sexual differentiation and gametogenesis multicellular eukaryotes. mRNA turnover were shown to influence stage-specific gene expression the protozoan Plasmodium. The DDX6-class RNA helicase, DOZI (development zygote inhibited), is found a complex with species cytoplasmic bodies female, blood-stage gametocytes. These translationally repressed complexes are normally stored for translation after fertilization. Genetic...
A universal feature of metazoan sexual development is the generation oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation translationally quiescent pools in female Plasmodium gametocytes depends on RNA helicase DOZI, but molecular machinery involved silencing transcripts these protozoans unknown. Using affinity purification coupled with mass-spectrometric analysis we identify...
BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy heterologous (different from vaccine), fewer doses, and at 24 weeks. METHODS: trial assessed tolerability, safety, immunogenicity, direct venous inoculation (DVI) or...
Malaria Cloak and Dagger Mosquitoes have a complex immune system capable of effective antiparasite responses; however, malaria transmission is still highly efficient. Molina-Cruz et al. (p. 984 , published online 9 May; see the Perspective by Philip Waters ) show that Plasmodium falciparum has gene product, Pfs47 makes parasite's ookinetes “invisible” to mosquito system. Disruption this mechanism could potentially be used block transmission.
Immune responses mounted by the malaria vector Anopheles gambiae are largely regulated Toll and Imd (immune deficiency) pathways via NF-kappaB transcription factors Rel1 Rel2, which controlled negative regulators Cactus Caspar, respectively. Rel1- Rel2-dependent in A. has been shown to be particularly critical mosquito's ability manage infection with rodent parasite Plasmodium berghei. Using RNA interference deplete of these pathways, we found that Rel2 controls resistance human falciparum,...
Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika (ZIKV), promoting increased ZIKV infection vitro. However, the correlation between vitro and vivo findings is not well characterized. Thus, we evaluated impact heterotypic flavivirus immunity on titers biofluids rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever were compared to flavivirus-naïve animals following a Brazilian strain. Sera from...
The Anopheles gambiae immune response against Plasmodium falciparum, an etiological agent of human malaria, has been identified as a source potential anti-Plasmodium genes and mechanisms to be exploited in efforts control the malaria transmission cycle. One such mechanism is Imd pathway, conserved signaling pathway that potent anti-P. falciparum activity. Silencing expression caspar, negative regulator or over-expressing rel2, pathway-controlled NFkappaB transcription factor, confers...
Significance The Anopheles gambiae mosquito is a very effective vector of human Plasmodium falciparum malaria. We recently found that the Pfs47 gene allows parasite to survive, by evading immune system. In this study, we explored mechanism evasion. inhibits Jun-N-terminal kinase-mediated activation apoptosis in invaded midgut cells preventing several caspases. Furthermore, lack caspase-S2 prevents induction enzymes potentiate epithelial nitration, reaction required for parasites be “visible”...
The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium infection through multiple molecular mechanisms. For example, midgut invasion by the parasite triggers an epithelial nitration response that promotes activation complement-like system. We found suppression JNK pathway, silencing either Hep, JNK, Jun or Fos expression, greatly enhanced infection; while overactivating this cascade, suppressor Puckered, had opposite effect. pathway via two coordinated responses. It...
From a forward genetic screen for phagocytosis mutants in Drosophila melanogaster , we identified mutation that affects peptidoglycan recognition protein (PGRP) SC1a and impairs the ability to phagocytose bacteria Staphylococcus aureus but not Escherichia coli Bacillus subtilis . Because of differences peptide linkages these bacteria, our data suggest PGRP-SC1a is necessary Lys-type typical most Gram + bacteria. also fail activate Toll/NF-κB signaling pathway are compromised survival after...
ABSTRACT To examine the hormonal and immunological mechanisms that mediate sex differences in susceptibility to malaria infection, intact gonadectomized (gdx) C57BL/6 mice were inoculated with Plasmodium chabaudi AS-infected erythrocytes, responses infection monitored. In addition reduced mortality, females recovered from infection-induced weigh loss anemia faster than males. Expression microarrays real-time reverse transcription-PCR revealed gonadally exhibited higher expression of...
A previous RTS,S/AS01B vaccine challenge trial demonstrated that a 3-dose (0-1-7-month) regimen with fractional third dose can produce high efficacy (VE) in adults challenged 3 weeks after vaccination. This study explored the VE of different delayed regimens adult and pediatric RTS,S/AS01 formulations.A total 130 participants were randomized into 5 groups. Four groups received doses or RTS,S/AS01E on 0-1-7-month schedule, final 1 2 being (one-fifth volume). One group full (month 0) 7)...
This protocol describes mosquito rearing in the insectary. The insectary rooms are maintained at 28°C and ~80% humidity, with a 12 hr. day/night cycle. For this procedure, you'll need cages, 10% sterile sucrose solution, paper towels, beaker, whatman filter paper, glass feeders, human blood serum, water bath, parafilm, distilled water, clean plastic trays, food (described below), net to cover vacuum, collection chamber collect adults.
Dengue virus (DENV) is transmitted by infectious mosquitoes during blood-feeding via saliva containing biologically-active proteins. Here, we examined the effect of varying DENV infection modality in rhesus macaques order to improve nonhuman primate (NHP) challenge model. NHPs were exposed DENV-1 subcutaneous or intradermal inoculation only, and salivary gland extract, mosquito feeding. The feeding group exhibited delayed onset viremia, greater viral loads, altered clinical immune responses...
Background Immunization with radiation-attenuated sporozoites (RAS) by mosquito bite provides >90% sterile protection against Plasmodium falciparum (Pf) malaria in humans. RAS invade hepatocytes but do not replicate. CD8+ T cells recognizing parasite-derived peptides on the surface of infected are likely primary protective mechanism. We conducted a randomized clinical trial immunization to assess safety, achieve 50% vaccine efficacy (VE) controlled human infection (CHMI), and generate...
The purpose of this procedure is to infect the Aedes mosquito with dengue virus in a laboratory condition and examine infection level dynamic tissues. This protocol routinely used for studying mosquito-virus interactions, especially identification novel host factors that are able determine vector competence. entire experiment must be conducted BSL2 laboratory. Similar Plasmodium falciparum infections, proper attire including gloves lab coat worn at all times. After experiment, materials came...
Abstract Our knowledge of Anopheles gambiae molecular biology has mainly been based on studies using inbred laboratory strains. Differences in the environmental exposure these and natural field mosquitoes have inevitably led to physiological divergences. We used global transcript abundance analyses probe into this divergence, identified patterns genes that provide insight specific adaptations caged mosquitoes. also compared gene profiles belonging two morphologically indistinguishable but...
Mosquito blood meals taken from humans and animals potentially represent a useful source of for the detection blood-borne pathogens. In this feasibility study, Anopheles stephensi mosquitoes were fed with spiked dengue virus type 2 (DENV-2) harvested at serial time points. These are not competent vectors, is expected to replicate. Ingested was spotted on Whatman FTA cards stored room temperature. abdomens removed −80°C. Control meal aliquots in vials or applied onto cards. After 4 weeks...
Background A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on efficacy (VE). We replaced chimpanzee 63 (ChAd63),...