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1.
Nat Commun ; 15(1): 5833, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992033

ABSTRACT

Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale.


Subject(s)
Antibodies, Viral , Arboviruses , Humans , Arboviruses/immunology , Arboviruses/isolation & purification , Animals , Antibodies, Viral/immunology , Antibodies, Viral/blood , Peptides/immunology , Peptides/chemistry , Zika Virus Infection/virology , Zika Virus Infection/immunology , Zika Virus Infection/blood , Zika Virus/immunology , Epitopes/immunology , Serologic Tests/methods , Arbovirus Infections/virology , Arbovirus Infections/immunology , Proteome , Colombia , Female , Peptide Library , Cell Surface Display Techniques , Male
2.
Vector Borne Zoonotic Dis ; 23(1): 9-17, 2023 01.
Article in English | MEDLINE | ID: mdl-36633562

ABSTRACT

Background: Bartonella species are fastidious gram-negative vector-borne bacteria with a wide range of mammalian reservoirs. While it is understood that some species of Bartonella are human pathogens, the extent of human exposure to Bartonella species (both pathogenic and nonpathogenic) is yet to be fully understood. Materials and Methods: To this end, residual sera from participants enrolled in undifferentiated fever studies in Cambodia, Ghana, Laos, and Peru were screened for the presence of IgG antibodies against Bartonella quintana and Bartonella henselae, using the FOCUS diagnostics Dual Spot- Bartonella IgG Immunofluorescence assay. Forty-eight patients with suspected or confirmed Bartonella bacilliformis exposure or infection in Peru were screened to assess cross-reactivity of the FOCUS assay for IgG against other Bartonella species. Results: Ten of 13 patients with confirmed B. bacilliformis infection were Bartonella-specific IgG positive, and overall, 36/48 of the samples were positive. In addition, 79/206, 44/200, 101/180, and 57/100 of the samples from Peru, Laos, Cambodia, and Ghana, respectively, were Bartonella-specific IgG positive. Furthermore, ectoparasite pools from Cambodia, Laos, and Peru were tested using quantitative real-time PCR (qPCR) for the presence of Bartonella DNA. Of the sand fly pools collected in Peru, 0/196 were qPCR positive; 15/140 flea pools collected in Cambodia were qPCR positive; while 0/105 ticks, 0/22 fleas, and 0/3 louse pools collected in Laos tested positive for Bartonella DNA. Conclusion: Evidence of Bartonella in fleas from Cambodia supports the possibility that humans are exposed to Bartonella through this traditional vector. However, Bartonella species were not found in fleas, ticks, or lice from Laos, or sand flies from Peru. This could account for the lower positive serology among the population in Laos and the strictly localized nature of B. bacilliformis infections in Peru. Human exposure to the Bartonella species and Bartonella as a human pathogen warrants further investigation.


Subject(s)
Bartonella Infections , Bartonella , Flea Infestations , Siphonaptera , Ticks , Humans , Animals , Bartonella/genetics , Bartonella Infections/epidemiology , Bartonella Infections/microbiology , Bartonella Infections/veterinary , Peru/epidemiology , Laos/epidemiology , Cambodia/epidemiology , Ghana , Flea Infestations/microbiology , Flea Infestations/veterinary , Siphonaptera/microbiology , Ticks/microbiology , Mammals
3.
Dalton Trans ; 47(35): 12459-12467, 2018 Sep 11.
Article in English | MEDLINE | ID: mdl-30140815

ABSTRACT

Bismuth oxyhalides (BiOX, where X = F, Cl, Br, I) are interesting materials due to their layered structure, which can be useful for different applications. In this work, we present the synthesis of the complete BiOX family in the thin film form. The tetragonal phase Bi2O3 film deposited onto a glass substrate was transformed into BiOF, BiOCl or BiOBr by a simple immersion at ambient temperature in a halide (X = F, Cl, Br) containing solution. For these films, a residual phase from the oxide was present and for BiOF another phase (tentatively identified as Bi7O5F11) was present too. For the BiOI film synthesis, an iodine and bismuth containing solution was sprayed onto the glass substrate heated at 275 °C and a pure phase was obtained. Microstructural and morphological characterization was performed by X-ray diffraction and scanning electron microscopy, while the chemical environment was studied by X-ray photoelectron spectroscopy. Optical and photocatalytic properties were also obtained. The physical and chemical characteristics of the BiOX films follow a correlation with the atomic radius of the halogen atom incorporated into the corresponding lattice. All the BiOX films showed a photocatalytic response for the photodiscoloration of indigo carmine dye under simulated sunlight irradiation in an alkaline medium. The photocatalytic reactions occurred via 2 proton-electron transfer from the oxide or oxyhalide to the adsorbed IC dye, favoring its reduction to the corresponding leuco IC form.

4.
MAbs ; 7(6): 1058-71, 2015.
Article in English | MEDLINE | ID: mdl-26337947

ABSTRACT

Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.


Subject(s)
Drug Design , ErbB Receptors/immunology , Immunoglobulin Light Chains/immunology , Single-Chain Antibodies/immunology , Amino Acid Sequence , Antibody Affinity/immunology , Humans , Immunoglobulin Light Chains/chemistry , Immunoglobulin Light Chains/genetics , Immunoglobulin kappa-Chains/chemistry , Immunoglobulin kappa-Chains/genetics , Immunoglobulin kappa-Chains/immunology , Immunoglobulin lambda-Chains/chemistry , Immunoglobulin lambda-Chains/genetics , Immunoglobulin lambda-Chains/immunology , Models, Molecular , Molecular Sequence Data , Mutation , Peptide Library , Protein Conformation , Protein Engineering/methods , Sequence Homology, Amino Acid , Single-Chain Antibodies/chemistry , Single-Chain Antibodies/genetics , Thermodynamics
5.
Int J Environ Health Res ; 19(5): 357-68, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19626518

ABSTRACT

Elevated indoor air pollution levels due to the burning of biomass in developing countries are well established. Few studies have quantitatively assessed air pollution levels of improved cookstoves and examined these measures in relation to health effects. We conducted a cross-sectional survey among 79 Honduran women cooking with traditional or improved cookstoves. Carbon monoxide and fine particulate matter (PM(2.5)) levels were assessed via indoor and personal monitoring. Pulmonary function and respiratory symptoms were ascertained. Finger-stick blood spot samples were collected to measure C-reactive protein (CRP) concentrations. The use of improved stoves was associated with 63% lower levels of personal PM(2.5), 73% lower levels of indoor PM(2.5), and 87% lower levels of indoor carbon monoxide as compared to traditional stoves. Women using traditional stoves reported symptoms more frequently than those using improved stoves. There was no evidence of associations between cookstove type or air quality measures with lung function or CRP.


Subject(s)
Air Pollution, Indoor/analysis , Cooking/instrumentation , Inhalation Exposure/analysis , Particulate Matter/analysis , Adult , Air Pollution, Indoor/prevention & control , C-Reactive Protein/metabolism , Carbon Monoxide/analysis , Carbon Monoxide/toxicity , Cooking/standards , Cross-Sectional Studies , Data Collection , Environmental Monitoring/methods , Female , Honduras , Housing , Humans , Inhalation Exposure/prevention & control , Middle Aged , Particulate Matter/toxicity , Respiratory Function Tests , Young Adult
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