Abstract. The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] ס 39.8-64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI ס 61.8-82.1) of P. vivax-infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 10 6 ) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.
Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 3 10 helical conformations in which enantiomeric left-and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a righthanded screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.
Successful communication: Two diastereotopic protons more than 60 bonds from the nearest chiral center appear as an AB system, showing that the intervening structure is a well‐ordered helix. Decay of anisochronicity quantifies the linear persistence of a helix of achiral amino acids: as little as 3.5 % of the chiral influence is lost with each additional achiral residue.
Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010-2013. Gold-mining was more prevalent in the departments of Antioquia, Córdoba, Bolívar, Chocó, Nariño, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelíbano, in Córdoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia.
BackgroundSignificant progress has been recently achieved in the development of Plasmodium vivax challenge infections in humans, which are essential for vaccine and drug testing. With the goal of accelerating clinical development of malaria vaccines, the outcome of infections experimentally induced in naïve and semi-immune volunteers by infected mosquito bites was compared.MethodsSeven malaria-naïve and nine semi-immune Colombian adults (n = 16) were subjected to the bites of 2–4 P. vivax sporozoite-infected Anopheles mosquitoes. Parasitemia levels, malaria clinical manifestations, and immune responses were assessed and compared.ResultsAll volunteers developed infections as confirmed by microscopy and RT-qPCR. No significant difference in the pre-patent period (mean 12.5 and 12.8 days for malaria-naïve and malaria-exposed, respectively) was observed but naïve volunteers developed classical malaria signs and symptoms, while semi-immune volunteers displayed minor or no symptoms at the day of diagnosis. A malaria-naïve volunteer developed a transient low submicroscopic parasitemia that cured spontaneously. Infection induced an increase in specific antibody levels in both groups.ConclusionSporozoite infectious challenge was safe and reproducible in semi-immune and naïve volunteers. This model will provide information for simultaneous comparison of the protective efficacy of P. vivax vaccines in naïve and semi-immune volunteers under controlled conditions and would accelerate P. vivax vaccine development.Trial Registrationclinicaltrials.gov NCT01585077
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