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1.
Alphonse Ouédraogo Alfred B. Tiono Désiré Kargougou Jean Baptiste Yaro Esperance Ouédraogo Youssouf Kaboré David Kangoye Edith C. Bougouma Adama Gansane Noelie Henri Amidou Diarra Souleymane Sanon Issiaka Soulama Amadou T. Konate Nora L. Watson Valerie Brown Jenny Hendriks Maria Grazia Pau Isabella Versteege Edison Wiesken Jerald Sadoff Issa Nebie Sodiomon B. Sirima 《PloS one》2013,8(11)
Background
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.Methods
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 109, 1010, 5X1010, 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.Results
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.Conclusion
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.Trial Registration
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459 相似文献2.
Metinee Wasoontharawat Sirima Suvarnakuta Jantama Sunthorn Kanchanatawee Kaemwich Jantama 《Bioprocess and biosystems engineering》2016,39(11):1775-1784
Rice straw (RS) may serve as a low-cost biomass for the production of biofuels and biochemicals, but its native structure is resistant to enzymatic and microbial deconstruction. Therefore, an efficient pre-treatment method is required to modify crystalline cellulose to a more reactive amorphous form. This work investigated pre-treatments of rice straw involving size reduction (S) followed by either sodium hydroxide (NaOH) or diluted sulfuric acid (H2SO4) and liquid hot water (LHW). The shrinkage of the vascular bundles in the rice straw structure pre-treated with NaOH–LHW–S was higher than that with LHW–S and H2SO4–LHW–S pre-treatments. The highest levels of total fermentative products and residual sugars were obtained at the concentrations of 7.8 ± 0.2 and 2.1 ± 0.3 g/L, respectively, after fermentation by Clostridium cellulolyticum for NaOH–LHW–S pre-treated rice straw at 121 °C for 120 min. Overall, the combined physicochemical pre-treatment of RS led to improved microbial hydrolysis during cellulose degradation at the percentage of 85.5 ± 0.5. 相似文献
3.
Villard V Agak GW Frank G Jafarshad A Servis C Nébié I Sirima SB Felger I Arevalo-Herrera M Herrera S Heitz F Bäcker V Druilhe P Kajava AV Corradin G 《PloS one》2007,2(7):e645
To identify malaria antigens for vaccine development, we selected alpha-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally "native" epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high alpha-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens. 相似文献
4.
5.
Bougouma EC Tiono AB Ouédraogo A Soulama I Diarra A Yaro JB Ouédaogo E Sanon S Konaté AT Nébié I Watson N Sanza M Dube TJ Sirima SB 《Malaria journal》2012,11(1):154
ABSTRACT: BACKGROUND: Genetic factors play a key role in determining resistance/susceptibility to infectious disease. Susceptibility of the human host to malaria infection has been reported to be influenced by genetic factors, which could be confounders if not taken into account in the assessment of the efficacy of interventions against malaria. This study aimed to assess the relationship between haemoglobin genotypes and malaria in children under five years in a site being characterized for future malaria vaccine trials. METHODS: The study population consisted of 452 children living in four rural villages. Hb genotype was determined at enrolment. Clinical malaria incidence was evaluated over a one-year period using combined active and passive surveillance. Prevalence of infection was evaluated via bi-annual cross-sectional surveys. At each follow-up visit, children received a brief clinical examination and thick and thin blood films were prepared for malaria diagnosis. A clinical malaria was defined as Plasmodium falciparum parasitaemia >2,500 parasites/ul and axillary temperature [greater than or equal to]37.5degreesC or reported fever over the previous 24 hours. RESULTS: Frequencies of Hb genotypes were 73.2% AA; 15.0% AC; 8.2% AS; 2.2% CC; 1.1% CS and 0.2% SS. Prevalence of infection at enrolment ranged from 61.9%-54.1% among AA, AC and AS children. After one year follow-up, clinical malaria incidence (95% CI) (episodes per person-year) was 1.9 (1.7-2.0) in AA, 1.6 (1.4-2.1) in AC, and 1.7 (1.4-2.0) in AS children. AC genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 1-2 years [rate ratio (95% CI) 0.66 (0.42-1.05)] and 2-3 years [rate ratio (95% CI) 0.37 (0.18-0.75)]; an association of opposite direction was however apparent among children aged 3-4 years. AS genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 2-3 years [rate ratio (95% CI) 0.63 (0.40-1.01)]. CONCLUSIONS: In this cohort of children, AC or AS genotype was associated with lower risk of clinical malaria relative to AA genotype only among children aged one to three years. It would be advisable for clinical studies of malaria in endemic regions to consider haemoglobin gene differences as a potentially important confounder, particularly among younger children. 相似文献
6.
Yamabhai M Emrat S Sukasem S Pesatcha P Jaruseranee N Buranabanyat B 《Journal of biotechnology》2008,133(1):50-57
Bacillus spp. are Gram-positive bacteria that secrete a large number of extracellular proteins of industrial relevance. In this report, three Bacillus extracellular hydrolytic enzymes, i.e., alpha-amylase, mannanase and chitinase, were cloned and over-expressed in Gram-negative Escherichia coli. We found that both the native signal peptides and that of E. coli outer membrane protein, OmpA, could be used to direct the secretion of the recombinant enzymes. The expressed enzymes were observed as clearing zones on agar plates or in zymograms. Determination of enzyme activities in different cell compartments suggested that the ability of the enzymes to be secreted out into the culture medium depends on the time of induction, the type of the signal peptides and the molecular mass of the enzymes. After overnight induction, most of the enzyme activities (85-96%) could be harvested from the culture supernatant. Our results suggest that various signal peptides of Bacillus spp. can be recognized by the E. coli secretion machinery. It seems possible that other enzymes with similar signal peptide could be secreted equally well in E. coli expression systems. Thus, our finding should be able to apply for cloning and extracellular production of other Bacillus hydrolytic enzymes as well as other proteins. 相似文献
7.
Rebekah van Bruggen Christian Gualtieri Alexandra Iliescu Chalisa Louicharoen Cheepsunthorn Punchalee Mungkalasut Jean-Fran?ois Trape David Modiano Bienvenu Sodiomon Sirima Pratap Singhasivanon Mark Lathrop Anavaj Sakuntabhai Jean-Fran?ois Bureau Philippe Gros 《PloS one》2015,10(12)
Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria. 相似文献
8.
Bamba Sanata Zida Adama Sangaré Ibrahim Sondo Apoline Cissé Mamoudou Sirima Constant Guiguemdé T. Robert Hennequin Christophe 《World journal of microbiology & biotechnology》2017,33(9):172
A cross-sectional study was conducted in Bobo-Dioulasso, Burkina Faso, to identify the yeast diversity associated with the manufacture of dolo, a traditional fermented beverage of Burkina Faso. From sixty specimens spread onto chromogenic medium plates, sixty-two strains were isolated then identified using MALDI-TOF analysis. Seven yeast species were identified, Saccharomyces cerevisiae (39%) followed by Pichia manshurica (18%) being the most frequent. Forty-three percent of the samples contained Candida species, notably Candida albicans. In conclusion, the combined use of a chromogenic medium and MALDI-TOF analysis reveals a higher diversity in yeast species present in the dolo than previously thought. 相似文献
9.
Sodiomon B. Sirima Alfred B. Tiono Alphonse Ouédraogo Amidou Diarra André Lin Ouédraogo Jean Baptiste Yaro Espérance Ouédraogo Adama Gansané Edith C. Bougouma Amadou T. Konaté Youssouf Kaboré Abdoulaye Traoré Chilengi Roma Issiaka Soulama Adrian J. F. Luty Simon Cousens Issa Nébié 《PloS one》2009,4(10)
Background
A Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe.The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12–24 months living in malaria endemic area of Burkina Faso.Methods
The study was a double-blind, randomized, controlled, dose escalation phase Ib trial, designed to assess the safety, reactogenicity and immunogenicity of three doses of either 15 or 30 µg of MSP3-LSP adsorbed on aluminum hydroxide in 45 children 12 to 24 months of age randomized into three equal groups. Each group received 3 vaccine doses (on days 0, 28 and 56) of either 15 µg of MSP3-LSP, 30 µg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were visited at home daily for the 6 days following each vaccination to solicit symptoms which might be related to vaccination. Serious adverse events occurring during the study period (1 year) were recorded. Antibody responses to MSP3-LSP were measured on days 0, 28, 56 and 84.Results
All 45 enrolled children received three MSP3 vaccine doses. No serious adverse events were reported. Most of the adverse events reported were mild to moderate in severity. The only reported local symptoms with grade 3 severity were swelling and induration, with an apparently dose related response. All grade 3 adverse events resolved without any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti-MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly the isotypes involved in the monocyte-dependent mechanism of P. falciparum parasite-killing.Conclusion
Our results support the promise of MSP3-LSP as a malaria vaccine candidate, both in terms of tolerability and of immunogenicity. Further assessment of the efficacy of this vaccine is recommended.Trial Registration
ClinicalTrials.gov NCT00452088相似文献10.
Lynn Grignard Bronner P. Gonçalves Angela M. Early Rachel F. Daniels Alfred B. Tiono Wamdaogo M. Guelbéogo Alphonse Ouédraogo Elke M. van Veen Kjerstin Lanke Amidou Diarra Issa Nebie Sodiomon B. Sirima Geoff A. Targett Sarah K. Volkman Daniel E. Neafsey Dyann F. Wirth Teun Bousema Chris Drakeley 《International journal for parasitology》2018,48(8):671-677
Plasmodium falciparum malaria infections often comprise multiple distinct parasite clones. Few datasets have directly assessed infection complexity in humans and mosquitoes they infect. Examining parasites using molecular tools may provide insights into the selective transmissibility of isolates. Using capillary electrophoresis genotyping and next generation amplicon sequencing, we analysed complexity of parasite infections in human blood and in the midguts of mosquitoes that became infected in membrane feeding experiments using the same blood material in two West African settings. Median numbers of clones in humans and mosquitoes were higher in samples from Burkina Faso (4.5, interquartile range 2–8 for humans; and 2, interquartile range 1–3 for mosquitoes) than in The Gambia (2, interquartile range 1–3 and 1, interquartile range 1–3, for humans and mosquitoes, respectively). Whilst the median number of clones was commonly higher in human blood samples, not all transmitted alleles were detectable in the human peripheral blood. In both study sample sets, additional parasite alleles were identified in mosquitoes compared with the matched human samples (10–88.9% of all clones/feeding assay, n?=?73 feeding assays). The results are likely due to preferential amplification of the most abundant clones in peripheral blood but confirm the presence of low density clones that produce transmissible sexual stage parasites. 相似文献