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  • 1
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    Online Resource
    A DNA Vaccine for Ebola Virus Is Safe and Immunogenic in a Phase I Clinical Trial
    American Society for Microbiology ; 2006
    In:  Clinical and Vaccine Immunology Vol. 13, No. 11 ( 2006-11), p. 1267-1277
    Details
    In: Clinical and Vaccine Immunology, American Society for Microbiology, Vol. 13, No. 11 ( 2006-11), p. 1267-1277
    Abstract: Ebola viruses represent a class of filoviruses that causes severe hemorrhagic fever with high mortality. Recognized first in 1976 in the Democratic Republic of Congo, outbreaks continue to occur in equatorial Africa. A safe and effective Ebola virus vaccine is needed because of its continued emergence and its potential for use for biodefense. We report the safety and immunogenicity of an Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as well as the nucleoprotein was evaluated in a randomized, placebo-controlled, double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were randomized to receive three injections of vaccine at 2 mg ( n = 5), 4 mg ( n = 8), or 8 mg ( n = 8) or placebo ( n = 6). Immunogenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well-tolerated, with no significant adverse events or coagulation abnormalities. Specific antibody responses to at least one of the three antigens encoded by the vaccine as assessed by ELISA and CD4 + T-cell GP-specific responses as assessed by ICS were detected in 20/20 vaccinees. CD8 + T-cell GP-specific responses were detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe and immunogenic in humans. Further assessment of the DNA platform alone and in combination with replication-defective adenoviral vector vaccines, in concert with challenge and immune data from nonhuman primates, will facilitate evaluation and potential licensure of an Ebola virus vaccine under the Animal Rule.
    Type of Medium: Online Resource
    ISSN: 1556-6811 , 1556-679X
    URL: Article
    DOI: 10.1128/CVI.00162-06
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2006
    detail.hit.zdb_id: 1496863-0
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  • 2
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    Deep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1
    American Society for Microbiology ; 2021
    In:  Journal of Virology Vol. 95, No. 3 ( 2021-01-13)
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 95, No. 3 ( 2021-01-13)
    Abstract: Exposure of the genital mucosa to a genetically diverse viral swarm from the donor HIV-1 can result in breakthrough and systemic infection by a single transmitted/founder (TF) virus in the recipient. The highly diverse HIV-1 envelope (Env) in this inoculating viral swarm may have a critical role in transmission and subsequent immune response. Thus, chronic (Env chronic ) and acute (Env acute ) Env chimeric HIV-1 were tested using multivirus competition assays in human mucosal penile and cervical tissues. Viral competition analysis revealed that Env chronic viruses resided and replicated mainly in the tissue, while Env acute viruses penetrated the human tissue and established infection of CD4 + T cells more efficiently. Analysis of the replication fitness, as tested in peripheral blood mononuclear cells (PBMCs), showed similar replication fitness of Env acute and Env chronic viruses, which did not correlate with transmission fitness in penile tissue. Further, we observed that chimeric Env viruses with higher replication in genital mucosal tissue (chronic Env viruses) had higher binding affinity to C-type lectins. Data presented herein suggest that the inoculating HIV-1 may be sequestered in the genital mucosal tissue (represented by chronic Env HIV-1) but that a single HIV-1 clone (e.g., acute Env HIV-1) can escape this trapped replication for systemic infection. IMPORTANCE During heterosexual HIV-1 transmission, a genetic bottleneck occurs in the newly infected individual as the virus passes from the mucosa, leading to systemic infection with a single transmitted HIV-1 clone in the recipient. This bottleneck in the recipient has just been described (K. Klein et al., PLoS Pathog 14:e1006754, https://doi.org/10.1371/journal.ppat.1006754 ), and the mechanisms involved in this selection process have not been elucidated. However, understanding mucosal restriction is of the utmost importance for understanding dynamics of infections and for designing focused vaccines. Using our human penile and cervical mucosal tissue models for mixed HIV infections, we provide evidence that HIV-1 from acute/early infection, compared to that from chronic infection, can more efficiently traverse the mucosal epithelium and be transmitted to T cells, suggesting higher transmission fitness. This study focused on the role of the HIV-1 envelope in transmission and provides strong evidence that HIV transmission may involve breaking the mucosal lectin trap.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01737-20
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1495529-5
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  • 3
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    Virulence Properties and Serotypes of Shiga Toxin-Producing Escherichia coli from Healthy Australian Cattle
    American Society for Microbiology ; 2002
    In:  Applied and Environmental Microbiology Vol. 68, No. 12 ( 2002-12), p. 6439-6445
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 68, No. 12 ( 2002-12), p. 6439-6445
    Abstract: The virulence properties and serotypes of complex Shiga toxin-producing Escherichia coli (cSTEC) were determined in two studies of healthy cattle in eastern Australia. In the first, a snapshot study, 84 cSTEC isolates were recovered from 37 of 1,692 (2.2%) fecal samples collected from slaughter-age cattle from 72 commercial properties. The second, a longitudinal study of three feedlots and five pasture beef properties, resulted in the recovery of 118 cSTEC isolates from 104 animals. Of the 70 serotypes identified, 38 had not previously been reported.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.68.12.6439-6445.2002
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2002
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 4
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    Serotypes and Virulence Gene Profiles of Shiga Toxin-Producing Escherichia coli Strains Isolated from Feces of Pasture-Fed and Lot-Fed Sheep
    American Society for Microbiology ; 2004
    In:  Applied and Environmental Microbiology Vol. 70, No. 7 ( 2004-07), p. 3910-3917
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 70, No. 7 ( 2004-07), p. 3910-3917
    Abstract: Shiga toxin-producing Escherichia coli (STEC) strains possessing genes for enterohemolysin ( ehxA ) and/or intimin ( eae ), referred to here as complex STEC (cSTEC), are more commonly recovered from the feces of humans with hemolytic uremic syndrome and hemorrhagic colitis than STEC strains that do not possess these accessory virulence genes. Ruminants, particularly cattle and sheep, are recognized reservoirs of STEC populations that may contaminate foods destined for human consumption. We isolated cSTEC strains from the feces of longitudinally sampled pasture-fed sheep, lot-fed sheep maintained on diets comprising various combinations of silage and grain, and sheep simultaneously grazing pastures with cattle to explore the diversity of cSTEC serotypes capable of colonizing healthy sheep. A total of 67 cSTEC serotypes were isolated, of which 21 (31.3%), mainly isolated from lambs, have not been reported. Of the total isolations, 58 (86.6%) were different from cSTEC serotypes isolated from a recent study of longitudinally sampled healthy Australian cattle (M. Hornitzky, B. A. Vanselow, K. Walker, K. A. Bettelheim, B. Corney, P. Gill, G. Bailey, and S. P. Djordjevic, Appl. Environ. Microbiol. 68: 6439-6445, 2002). Our data suggest that cSTEC serotypes O5:H − , O75:H8, O91:H − , O123:H − , and O128:H2 are well adapted to colonizing the ovine gastrointestinal tract, since they were the most prevalent serotypes isolated from both pasture-fed and lot-fed sheep. Collectively, our data show that Australian sheep are colonized by diverse cSTEC serotypes that are rarely isolated from healthy Australian cattle.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.70.7.3910-3917.2004
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 5
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    Virulence Properties and Serotypes of Shiga Toxin-Producing Escherichia coli from Healthy Australian Slaughter-Age Sheep
    American Society for Microbiology ; 2001
    In:  Journal of Clinical Microbiology Vol. 39, No. 5 ( 2001-05), p. 2017-2021
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 39, No. 5 ( 2001-05), p. 2017-2021
    Abstract: A group of 1,623 ovine fecal samples recovered from 65 geographically distinct mutton sheep and prime lamb properties across New South Wales, Australia, were screened for the presence of Shiga toxin-producing Escherichia coli (STEC) virulence factors ( stx 1 , stx 2 , eaeA , and ehxA ). A subset was cultured for STEC isolates containing associated virulence factors ( eaeA and/or ehxA ), which were isolated from 17 of 20 (85%) and 19 of 20 (95%) tested prime lamb and mutton sheep properties, respectively. STEC isolates containing stx 1 , stx 2 , and ehxA were most commonly isolated (19 of 40 flocks; 47.5%), and this profile was observed for 10 different serotypes. Among 90 STEC isolates studied, the most common serotypes were O91:H − (22 isolates [24.4%]), O5:H − (16 isolates [17.8%]), O128:H2 (11 isolates [12.2%] ), O123:H − (8 isolates [8.9%]), and O85:H49 (5 isolates [5.6%] ). Two isolates (2.2%) were typed as O157:H − . A total of 78 of 90 STEC isolates (86.7%) expressed Shiga toxin in Vero cell culture and 75 of 84 ehxA -positive isolates (89.3%) expressed enterohemolysin on washed sheep blood agar. eaeA was observed in 11 of 90 (12.2%) ovine STEC isolates, including serotypes O5:H − , O84:H − , O85:H49, O123:H − O136:H40, and O157:H − . Although only 2 of 90 isolates were typed as O157:H − , the predominant serotypes recovered during this study have been recovered from human patients with clinical disease, albeit rarely.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.39.5.2017-2021.2001
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 6
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    Protective Cytotoxic T-Cell Responses Induced by Venezuelan Equine Encephalitis Virus Replicons Expressing Ebola Virus Proteins
    American Society for Microbiology ; 2005
    In:  Journal of Virology Vol. 79, No. 22 ( 2005-11-15), p. 14189-14196
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 79, No. 22 ( 2005-11-15), p. 14189-14196
    Abstract: Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that antibody-mediated protection could only be demonstrated after vaccination against the glycoprotein. In this study, the murine CD8 + T-cell responses to six Ebola virus proteins were examined. CD8 + T cells specific for Ebola virus glycoprotein, nucleoprotein, and viral proteins (VP24, VP30, VP35, and VP40) were identified by intracellular cytokine assays using splenocytes from vaccinated mice. The cells were expanded by restimulation with peptides and demonstrated cytolytic activity. Adoptive transfer of the CD8 + cytotoxic T cells protected filovirus naïve mice from challenge with Ebola virus. These data support a role for CD8 + cytotoxic T cells as part of a protective mechanism induced by vaccination against six Ebola virus proteins and provide additional evidence that cytotoxic T-cell responses can contribute to protection from filovirus infections.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.79.22.14189-14196.2005
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2005
    detail.hit.zdb_id: 1495529-5
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  • 7
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    Isolation of a Potently Neutralizing and Protective Human Monoclonal Antibody Targeting Yellow Fever Virus
    American Society for Microbiology ; 2022
    In:  mBio Vol. 13, No. 3 ( 2022-06-28)
    Details
    In: mBio, American Society for Microbiology, Vol. 13, No. 3 ( 2022-06-28)
    Abstract: Yellow fever virus (YFV) causes sporadic outbreaks of infection in South America and sub-Saharan Africa. While live-attenuated yellow fever virus vaccines based on three substrains of 17D are considered some of the most effective vaccines in use, problems with production and distribution have created large populations of unvaccinated, vulnerable individuals in areas of endemicity. To date, specific antiviral therapeutics have not been licensed for human use against YFV or any other related flavivirus. Recent advances in monoclonal antibody (mAb) technology have allowed the identification of numerous candidate therapeutics targeting highly pathogenic viruses, including many flaviviruses. Here, we sought to identify a highly neutralizing antibody targeting the YFV envelope ( E ) protein as a therapeutic candidate. We used human B cell hybridoma technology to isolate mAbs from circulating memory B cells from human YFV vaccine recipients. These antibodies bound to recombinant YFV E protein and recognized at least five major antigenic sites on E . Two mAbs (designated YFV-136 and YFV-121) recognized a shared antigenic site and neutralized the YFV-17D vaccine strain in vitro . YFV-136 also potently inhibited infection by multiple wild-type YFV strains, in part, at a postattachment step in the virus replication cycle. YFV-136 showed therapeutic protection in two animal models of YFV challenge, including hamsters and immunocompromised mice engrafted with human hepatocytes. These studies define features of the antigenic landscape of the YFV E protein recognized by the human B cell response and identify a therapeutic antibody candidate that inhibits infection and disease caused by highly virulent strains of YFV. IMPORTANCE Yellow fever virus (YFV) is a mosquito-borne virus that occasionally causes outbreaks of severe infection and disease in South America and sub-Saharan Africa. There are very effective live-attenuated (weakened) yellow fever virus vaccines, but recent problems with their production and distribution have left many people in affected areas vulnerable. Here, we sought to isolate an antibody targeting the surface of the virus for possible use in the future as a biologic drug to prevent or treat YFV infection. We isolated naturally occurring antibodies from individuals who had received a YFV vaccine. We created antibodies and tested them. We found that the antibody with the most powerful antiviral activity was a beneficial treatment in two different small-animal models of human infection. These studies identified features of the virus that are recognized by the human immune system and generated a therapeutic antibody candidate that inhibits infection caused by highly virulent strains of YFV.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mbio.00512-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2557172-2
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  • 8
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    Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s
    American Society for Microbiology ; 2023
    In:  mSphere
    Details
    In: mSphere, American Society for Microbiology
    Abstract: Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an “adult-like” response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This “adult-like” response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    URL: Article
    DOI: 10.1128/msphere.00451-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2844248-9
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  • 9
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    Novel Microbial Assemblages Dominate Weathered Sulfide-Bearing Rock from Copper-Nickel Deposits in the Duluth Complex, Minnesota, USA
    American Society for Microbiology ; 2017
    In:  Applied and Environmental Microbiology Vol. 83, No. 16 ( 2017-08-15)
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 83, No. 16 ( 2017-08-15)
    Abstract: The Duluth Complex in northeastern Minnesota hosts economically significant deposits of copper, nickel, and platinum group elements (PGEs). The primary sulfide mineralogy of these deposits includes the minerals pyrrhotite, chalcopyrite, pentlandite, and cubanite, and weathering experiments show that most sulfide-bearing rock from the Duluth Complex generates moderately acidic leachate (pH 4 to 6). Microorganisms are important catalysts for metal sulfide oxidation and could influence the quality of water from mines in the Duluth Complex. Nevertheless, compared with that of extremely acidic environments, much less is known about the microbial ecology of moderately acidic sulfide-bearing mine waste, and so existing information may have little relevance to those microorganisms catalyzing oxidation reactions in the Duluth Complex. Here, we characterized the microbial communities in decade-long weathering experiments (kinetic tests) conducted on crushed rock and tailings from the Duluth Complex. Analyses of 16S rRNA genes and transcripts showed that differences among microbial communities correspond to pH, rock type, and experimental treatment. Moreover, microbial communities from the weathered Duluth Complex rock were dominated by taxa that are not typically associated with acidic mine waste. The most abundant operational taxonomic units (OTUs) were from the genera Meiothermus and Sulfuriferula , as well as from diverse clades of uncultivated Chloroflexi , Acidobacteria , and Betaproteobacteria . Specific taxa, including putative sulfur-oxidizing Sulfuriferula spp., appeared to be primarily associated with Duluth Complex rock, but not pyrite-bearing rocks subjected to the same experimental treatment. We discuss the implications of these results for the microbial ecology of moderately acidic mine waste with low sulfide content, as well as for kinetic testing of mine waste. IMPORTANCE Economic sulfide mineral deposits in the Duluth Complex may represent the largest undeveloped source of copper and nickel on Earth. Microorganisms are important catalysts for sulfide mineral oxidation, and research on extreme acidophiles has improved our ability to manage and remediate mine wastes. We found that the microbial assemblages associated with weathered rock from the Duluth Complex are dominated by organisms not widely associated with mine waste or mining-impacted environments, and we describe geochemical and experimental influences on community composition. This report will be a useful foundation for understanding the microbial biogeochemistry of moderately acidic mine waste from these and similar deposits.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.00909-17
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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  • 10
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    Variation in the Microbiota of Ixodes Ticks with Regard to Geography, Species, and Sex
    American Society for Microbiology ; 2015
    In:  Applied and Environmental Microbiology Vol. 81, No. 18 ( 2015-09-15), p. 6200-6209
    Details
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 81, No. 18 ( 2015-09-15), p. 6200-6209
    Abstract: Ixodes scapularis is the principal vector of Lyme disease on the East Coast and in the upper Midwest regions of the United States, yet the tick is also present in the Southeast, where Lyme disease is absent or rare. A closely related species, I. affinis , also carries the pathogen in the South but does not seem to transmit it to humans. In order to better understand the geographic diversity of the tick, we analyzed the microbiota of 104 adult I. scapularis and 13 adult I. affinis ticks captured in 19 locations in South Carolina, North Carolina, Virginia, Connecticut, and New York. Initially, ticks from 4 sites were analyzed by 454 pyrosequencing. Subsequently, ticks from these sites plus 15 others were analyzed by sequencing with an Illumina MiSeq machine. By both analyses, the microbiomes of female ticks were significantly less diverse than those of male ticks. The dissimilarity between tick microbiomes increased with distance between sites, and the state in which a tick was collected could be inferred from its microbiota. The genus Rickettsia was prominent in all locations. Borrelia was also present in most locations and was present at especially high levels in one site in western Virginia. In contrast, members of the family Enterobacteriaceae were very common in North Carolina I. scapularis ticks but uncommon in I. scapularis ticks from other sites and in North Carolina I. affinis ticks. These data suggest substantial variations in the Ixodes microbiota in association with geography, species, and sex.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
    URL: Article
    DOI: 10.1128/AEM.01562-15
    RVK:
    WA 15000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2015
    detail.hit.zdb_id: 223011-2
    detail.hit.zdb_id: 1478346-0
    SSG: 12
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