Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications

The first human vaccines against the malaria parasite have been designed to elicit antibodies to the circumsporozoite protein of Plasmodium falciparum. However, it is not known whether any level of naturally acquired antibodies to the circumsporozoite protein can predict resistance to Plasmodium falciparum malaria. In this study, 83 adults in a malaria-endemic region of Kenya were tested for circumsporozoite antibodies and then treated for malaria. They were monitored for the development of new malaria infections for 98 days. Antibody levels, as determined by four assays in vitro, were indistinguishable between the 60 individuals who did and the 23 who did not develop parasitemia during follow-up, and there was no apparent relation between day of onset of parasitemia and level of antibodies to circumsporozoite protein. Unless immunization with sporozoite vaccines induces antibodies that are quantitatively or qualitatively superior to the circumsporozoite antibodies in these adults, it is unlikely that such antibodies will prevent infection in areas with as intense malaria transmission as western Kenya.     

Circumsporozoite protein heterogeneity in the human malaria parasite Plasmodium vivax

Phenotypic heterogeneity in the repetitive portion of a human malaria circumsporozoite (CS) protein, a major target of candidate vaccines, has been found. Over 14% of clinical cases of uncomplicated Plasmodium vivax malaria at two sites in western Thailand produced sporozoites immunologically distinct from previously characterized examples of the species. Monoclonal antibodies to the CS protein of other P. vivax isolates and to other species of human and simian malarias did not bind to these nonreactive sporozoites, nor did antibodies from monkeys immunized with a candidate vaccine made from the repeat portion of a New World CS protein. The section of the CS protein gene between the conserved regions I and II of a nonreactive isolate contained a nonapeptide repeat, Ala-Asn-Gly-Ala-Gly-Asn-Gln-Pro-Gly, identical at only three amino acid positions with published nonapeptide sequences. This heterogeneity implies that a P. vivax vaccine based on the CS protein repeat of one isolate will not be universally protective.     

Studies on the comparative effectiveness of permethrin and deet against bloodsucking arthropods

A comparison was made of the effectiveness of permethrin and deet against Ornithodoros parkeri (Acari: Argasidae), Leptotrombidium fletcheri (Acari: Trombiculidae), Rhodnius prolixus (Heteroptera: Reduviidae), Phlebotomus papatasi and Lutzomyia longipalpis (Diptera: Psychodidae), Anopheles Stephensi, Anopheles albimanus, Aedes taeniorhynchus, Aedes aegypti and Culex pipiens (Diptera: Culicidae), Glossina morsitans (Diptera: Glossinidae) and Xenopsylla cheopis (Siphonaptera: Pulicidae), using dose-response methods. At the ED₉₅ (95% effective dose) level, deet was more potent (P<0.05) than permethrin against all species except O. parkeri and R. prolixus. In addition, the slope of the dose-response line for deet was greater than that for permethrin against all species except O. parkeri and R. prolixus. Permethrin exhibited repellent and/or toxic effects, depending on the dose used and the individual tolerances of members of the insect test population.     

Eine Fliege (Pegomyia rubivora Coquillet) als Himbeerschädling

Ohne Zusammenfassung     

Rheological Properties of Vital Wheat Gluten Suspensions

Flour and doughs represent rheologically complex materials whose properties are dependent on many factors including processing conditions. To avoid some of the problems associated with the rheological characterization of dough, we have initiated a study focused on the rheological properties of one of the major components of dough, vital wheat gluten. Suspensions of vital wheat gluten were prepared with concentrations of 225–325 mg/mL.The moduli of the gluten suspensions was 0.2 Pa at 225 mg/mL to 37 Pa at 325 mg/mL. At <250 mg/mL, the gluten suspensions exhibited fluidlike behavior. The crossover frequency, (G′[ω] = G″[ω]) shifted slightly from 0.5 rad/sec at 225 mg/mL to 0.9 rad/sec at 250 mg/mL. At >300 mg/mL, the gluten suspensions exhibited solidlike behavior. The crossover frequencies were independent of concentration and equal to 100 rad/sec. At <250 mg/mL, the high‐frequency behavior of moduli were proportional to ω^3/4, as expected for a semiflexible coil. At >300 mg/mL, the high‐frequency behavior of moduli were proportional to ω^1/2, indicating a flexible coil. These results suggest vital wheat gluten suspensions undergo a structural change between 250 and 300 mg/mL.     

Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.     

Fenhexamid - an efficient and inexpensive fungicide for selection of Magnaporthe oryzae transformants

European Journal of Plant Pathology - Magnaporthe oryzae is one of the most economically important phytopathogenic fungi, and is used as a model organism to study plant-pathogen interactions. To...     

An RNA ligase essential for RNA editing and survival of the bloodstream form of Trypanosoma brucei

RNA editing in trypanosomes occurs by a series of enzymatic steps that are catalyzed by a macromolecular complex. The TbMP52 protein is shown to be a component of this complex, to have RNA ligase activity, and to be one of two adenylatable proteins in the complex. Regulated repression of TbMP52 blocks editing, which shows that it is a functional component of the editing complex. This repression is lethal in bloodforms of the parasite, indicating that editing is essential in the mammalian stage of the life cycle. The editing complex, which is present in all kinetoplastid parasites, may thus be a chemotherapeutic target.     

Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides

Proteosomes are hydrophobic, membranous, multimolecular preparations of meningococcal outer membrane proteins that are also B cell mitogens. These characteristics suggested that proteosomes may serve as carrier proteins and adjuvants to enhance peptide immunogenicity. Although high titers of malaria circumsporozoite (CS) antibodies protect against malaria, vaccines thus far tested in humans have been insufficiently immunogenic to be clinically useful. Here it is shown that synthetic CS peptides hydrophobically complexed to proteosomes by way of lauroyl-cysteine become highly immunogenic in mice without other adjuvants. The high titers of antibodies produced and the safety of proteosomes in humans suggest that this novel system is widely applicable for the development of peptide vaccines to protect against many diseases.