Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

Background

A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-1₁₉, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175.

Method

Healthy malaria naïve Indian male subjects aged 18–45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10μg, 25μg and 50μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180.

Results

JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-1₁₉. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain.

Conclusion

Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-1₁₉ construct needs to be optimised to improve its immunogenicity.

Trial Registration

Clinical Trial Registry, India CTRI/2010/091/000301     

Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency

We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10⁻⁴, nucleotide diversity of 1.6×10⁻³ for CEU and 3.7×10⁻³ for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.     

Peptide Similarity Search Based and Virtual Screening Based Strategies to Identify Small Molecules to Inhibit CarD–RNAP Interaction in M. tuberculosis

International Journal of Peptide Research and Therapeutics - Inhibition of protein–protein interaction is considered as an innovative approach in the drug development field. In the present...     

A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome

A model of DNA sequence evolution applicable to coding regions is presented. This represents the first evolutionary model that accounts for dependencies among nucleotides within a codon. The model uses the codon, as opposed to the nucleotide, as the unit of evolution, and is parameterized in terms of synonymous and nonsynonymous nucleotide substitution rates. One of the model's advantages over those used in methods for estimating synonymous and nonsynonymous substitution rates is that it completely corrects for multiple hits at a codon, rather than taking a parsimony approach and considering only pathways of minimum change between homologous codons. Likelihood-ratio versions of the relative-rate test are constructed and applied to data from the complete chloroplast DNA sequences of Oryza sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these tests confirm previous findings that substitution rates in the chloroplast genome are subject to both lineage-specific and locus-specific effects. Additionally, the new tests suggest tha the rate heterogeneity is due primarily to differences in nonsynonymous substitution rates. Simulations help confirm previous suggestions that silent sites are saturated, leaving no evidence of heterogeneity in synonymous substitution rates.      

Levels of acute phase proteins remain stable after ischemic stroke

Background  

Inflammation and inflammatory biomarkers play an important role in atherosclerosis and cardiovascular disease. Little information is available, however, on time course of serum markers of inflammation after stroke.     

Heterotrophic utilization of extracellular products of phytoplankton in a tropical estuary

Bacterial uptake of algal exudates has been estimated in a tropicalestuary, Dona Paula, where the seasonal fluctuations in hydrographicand nutrient parameters as well as dissolved organic matterconcentrations and phytoplankton species composition are dominatedby the monsoon regime. A close coupling existed between algaland bacterial trophic levels. Algal exudation products wererapidly assimilated with short turnover times. An average 80%of the excreted material was removed by heterotrophic bacteriaand there was a significant correlation between algal extracellularproduction and net bacterial uptake of algal exudates.     

Exopolysaccharides of Pseudomonas mendocina P2d

Pseudomonas mendocina P₂d cells grown at room temperature in sodium benzoate as sole source of carbon, followed by storage on ice, form a viscous pellet on centrifugation. Such viscosity is not produced by cells grown on glucose or any other carbohydrates. Viscosity was found to be associated with the extracellular polysaccharide (EPS) of cells and not released into the supernatant fluid. A combination of sodium dodecyl sulphate-citrate buffer and homogenization was effective in releasing the EPS. The EPS is a heteropolysaccharide, consisting of rhamnose, fucose, glucose, ribose, arabinose and mannose, which has good emulsifying activity.     

Insect drift over the northern Arabian sea in early summer

Air borne insects, mostly carried by wind currents, were trapped over the northern Arabian sea (16‡ to 20‡ N; 68‡ to 72‡ E), in the course of cruise No. 111, ORVSAGAR KANYA (March 14 to April 7, 1996). A total of 2,301 insects belonging to 8 different orders, 47 families and 173 species were trapped. Of these, Hymenoptera was represented by the largest number (1082), which was followed by Hemiptera (586), Diptera (552), Coleoptera (51), Neuroptera (10), Trichoptera (03), Lepidoptera (03) and Orthoptera (01). The trapped insects were mostly between 0.6 mm to over 11 mm long. The data was examined for α-diversity as well as for possible correlations between various parameters like the diversity index, size and number of insects trapped on one hand and the distance of the nearest land mass in wind direction, on the other. Deceased.