48 research outputs found

    Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus variants

    Get PDF
    As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta, or Delta variants, we showed that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta Plus (Delta+), which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting that the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+, and Omicron, which all possess the N417 residue. We isolated an N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D MAb utilized the IGHV3-23*01 germ line gene and had somatic hypermutations similar to those of previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targeting escape mutations, such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines. IMPORTANCE : The evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring various immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants and to define shared epitopes. We show that Beta and Delta infections resulted in antibody responses that were more cross-reactive than the original D614G variant, but they had differing patterns of cross-reactivity. We further isolated an antibody from Beta infection which targeted the N417 site, enabling cross-neutralization of Beta, Delta+, and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.The South African Research Chairs Initiative of the Department of Science and Innovation, the National Research Foundation of South Africa, the SA Medical Research Council SHIP program and the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program.https://journals.asm.org/journal/jvihj2023ImmunologyInternal Medicin

    Cross-reactive neutralizing antibody responses elicited by SARS-CoV-2 501Y.V2 (B.1.351)

    Get PDF
    No abstract available.The South African Medical Research Council, the Centers for Disease Control and Prevention, the ELMA South Africa Foundation, the Wellcome Trust, the Fogarty International Center of the National Institutes of Health, the FLAIR Fellowship program, the European and Developing Countries Clinical Trials Partnership 2 of the European Union Horizon 2020 program, the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation.http://www.nejm.orgam2022Internal Medicin

    The retrospective analysis of Antarctic tracking data project

    Get PDF
    The Retrospective Analysis of Antarctic Tracking Data (RAATD) is a Scientific Committee for Antarctic Research project led jointly by the Expert Groups on Birds and Marine Mammals and Antarctic Biodiversity Informatics, and endorsed by the Commission for the Conservation of Antarctic Marine Living Resources. RAATD consolidated tracking data for multiple species of Antarctic meso- and top-predators to identify Areas of Ecological Significance. These datasets and accompanying syntheses provide a greater understanding of fundamental ecosystem processes in the Southern Ocean, support modelling of predator distributions under future climate scenarios and create inputs that can be incorporated into decision making processes by management authorities. In this data paper, we present the compiled tracking data from research groups that have worked in the Antarctic since the 1990s. The data are publicly available through biodiversity.aq and the Ocean Biogeographic Information System. The archive includes tracking data from over 70 contributors across 12 national Antarctic programs, and includes data from 17 predator species, 4060 individual animals, and over 2.9 million observed locations

    SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals

    Get PDF
    The SARS-CoV-2 Omicron variant escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers cross-reactive humoral responses to other variants of concern (VOCs) remains unknown. We used plasma from 20 unvaccinated and 7 vaccinated individuals infected by Omicron BA.1 to test binding, Fc effector function, and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies targeted Omicron and other VOCs at comparable levels. However, Omicron BA.1- triggered neutralization was not extensively cross-reactive for VOCs (14- to 31-fold titer reduction), and we observed 4-fold decreased titers against Omicron BA.2. In contrast, vaccination followed by breakthrough Omicron infection associated with improved cross-neutralization of VOCs with titers exceeding 1:2,100. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Although Omicron-based immunogens might be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2-naive individuals.The South African Research Chairs Initiative of the Department of Science and Innovation, the National Research Foundation of South Africa, the South African Medical Research Council Strategic Health Innovation Partnerships (SHIP) program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA), the Bill and Melinda Gates Foundation through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program and L’Oreal/UNESCO Women in Science South Africa Young Talents award.http://www.cell.com/cell-host-microbe/homeam2023ImmunologyMedical Virolog

    Species distribution and antifungal susceptibility patterns of Candida isolates from a public tertiary teaching hospital in the Eastern Cape Province, South Africa

    Get PDF
    vital:49389Candida species are the leading cause of invasive fungal infections, and over the past decade there has been an increased isolation of drug resistant Candida species. This study aimed to identify the species distribution of Candida isolates and to determine their unique antifungal susceptibility and resistance patterns. During a cross-sectional study, 209 Candida isolates (recovered from 206 clinical samples) were collected and their species distribution was determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa) was used to determine minimum inhibitory concentrations (MICs) to azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes (amphotericin B) and flucytosine. Four species of Candida were isolated, of which C. albicans was the most frequent, isolated in 45.4 percent (95/209) of the isolates, followed by C. glabrata: 31.1 percent (65/209). The MICs of the different antifungal drugs varied amongst the species of Candida. From the 130 isolates tested for MICs, 90.77 percent (112/130) were susceptible to all antifungal drugs and 6.9 percent (9/130) of the isolates were multi-drug resistant. C. dubliniensis (n=2) isolates were susceptible to all the above mentioned antifungal drugs. There was no significant difference in species distribution amongst clinical specimens and between patients’ genders (P40.05). An increase in MIC values for fluconazole and flucytosine towards the resistance range was observed. To our knowledge, this is the first report on surveillance of Candida species distribution and antifungal susceptibility at a public tertiary teaching hospital in Eastern Cape, South Africa. Key words: Candida species; Distribution; Antifungal susceptibility; Identification; South Afric

    The retrospective analysis of Antarctic tracking data project

    Get PDF
    The Retrospective Analysis of Antarctic Tracking Data (RAATD) is a Scientific Committee for Antarctic Research project led jointly by the Expert Groups on Birds and Marine Mammals and Antarctic Biodiversity Informatics, and endorsed by the Commission for the Conservation of Antarctic Marine Living Resources. RAATD consolidated tracking data for multiple species of Antarctic meso- and top-predators to identify Areas of Ecological Significance. These datasets and accompanying syntheses provide a greater understanding of fundamental ecosystem processes in the Southern Ocean, support modelling of predator distributions under future climate scenarios and create inputs that can be incorporated into decision making processes by management authorities. In this data paper, we present the compiled tracking data from research groups that have worked in the Antarctic since the 1990s. The data are publicly available through biodiversity.aq and the Ocean Biogeographic Information System. The archive includes tracking data from over 70 contributors across 12 national Antarctic programs, and includes data from 17 predator species, 4060 individual animals, and over 2.9 million observed locations.Supplementary Figure S1: Filtered location data (black) and tag deployment locations (red) for each species. Maps are Lambert Azimuthal projections extending from 90° S to 20° S.Supplementary Table S1: Names and coordinates of the major study sites in the Southern Ocean and on the Antarctic Continent where tracking devices were deployed on the selected species (indicated by their 4-letter codes in the last column).Online Table 1: Description of fields (column names) in the metadata and data files.Supranational committees and organisations including the Scientific Committee on Antarctic Research Life Science Group and BirdLife International. National institutions and foundations, including but not limited to Argentina (Dirección Nacional del Antártico), Australia (Australian Antarctic program; Australian Research Council; Sea World Research and Rescue Foundation Inc., IMOS is a national collaborative research infrastructure, supported by the Australian Government and operated by a consortium of institutions as an unincorporated joint venture, with the University of Tasmania as Lead Agent), Belgium (Belgian Science Policy Office, EU Lifewatch ERIC), Brazil (Brazilian Antarctic Programme; Brazilian National Research Council (CNPq/MCTI) and CAPES), France (Agence Nationale de la Recherche; Centre National d’Etudes Spatiales; Centre National de la Recherche Scientifique; the French Foundation for Research on Biodiversity (FRB; www.fondationbiodiversite.fr) in the context of the CESAB project “RAATD”; Fondation Total; Institut Paul-Emile Victor; Programme Zone Atelier de Recherches sur l’Environnement Antarctique et Subantarctique; Terres Australes et Antarctiques Françaises), Germany (Deutsche Forschungsgemeinschaft, Hanse-Wissenschaftskolleg - Institute for Advanced Study), Italy (Italian National Antarctic Research Program; Ministry for Education University and Research), Japan (Japanese Antarctic Research Expedition; JSPS Kakenhi grant), Monaco (Fondation Prince Albert II de Monaco), New Zealand (Ministry for Primary Industries - BRAG; Pew Charitable Trusts), Norway (Norwegian Antarctic Research Expeditions; Norwegian Research Council), Portugal (Foundation for Science and Technology), South Africa (Department of Environmental Affairs; National Research Foundation; South African National Antarctic Programme), UK (Darwin Plus; Ecosystems Programme at the British Antarctic Survey; Natural Environment Research Council; WWF), and USA (U.S. AMLR Program of NOAA Fisheries; US Office of Polar Programs).http://www.nature.com/sdataam2021Mammal Research Institut

    Barriers to tuberculosis and human immunodeficiency virus treatment guidelines adherence among nurses initiating and managing anti-retroviral therapy in KwaZulu-Natal and North West provinces

    No full text
    Background: Nurses, as front-line care providers in the South Africa’s health care system, are called upon to deliver integrated interventions for tuberculosis and human immunodeficiency virus (TB and HIV) including nurse-initiated management of anti-retroviral therapy (NIMART) and anti-TB treatment. Adherence to treatment guidelines and factors associated with non-adherence to treatment guidelines among nurses remain under explored. Purpose: To explore and describe barriers to treatment guidelines adherence among nurses initiating and managing anti-retroviral therapy and anti-TB treatment in KwaZulu-Natal and North West provinces. Design: This study employed a qualitative exploratory descriptive design. Methods: Four semi-structured focus group interviews were conducted during 2014 each consisting of four to eight NIMART trained nurses. Audiotaped interviews were transcribed verbatim and analysed using Atlas T.I. software. Findings: During data analysis, two themes emerged: (1) NIMART trained nurses’ distress about TB and HIV guidelines adherence that is inclusive of lack of agreement with guidelines, poor motivation to implement guidelines, poor clinical support and supervision, resistance to change, insufficient knowledge or lack of awareness and (2) exterior factors inhibiting nurses’ adherence to treatment guidelines which incorporated organisational factors, guidelines-related factors and patient-related factors. Conclusion: This qualitative study identified that nurses have substantial concerns over guideline adherence. If NIMART trained nurses’ barriers inhibiting adherence to treatment guidelines cannot be remedied, patient outcomes may suffer and South Africa will struggle to meet the 90-90-90 targets

    Comparison of trauma on survivors of sexual assault and intimate partner violence in Limpopo

    No full text
    Background: Gender-based violence is a challenge in South Africa, despite available interventions. Caring for the survivors of both forms of violence is critical for ensuring their speedy recovery. Objectives: To compare the effects of trauma on female survivors of sexual assault versus those experienced by survivors of physical assault by their intimate partners. Method: A quantitative cross-sectional comparative study design was used to compare 30 sexually-assaulted women and 30 physically-assaulted women regarding depressive symptoms, posttraumatic stress disorder and coping styles three months after the incident. Semi-structured interviews were conducted with the survivors of both types of assault and the Beck Depression Inventory posttraumatic stress disorder checklist and Brief COPE Inventory were administered in order to obtain quantitative data. Both parametric and non-parametric statistics were employed. Ethical measures were adhered to throughout the research process. Results: A significantly-higher proportion of sexually-assaulted women disclosed the incident to family (p = 0.021). The majority of sexually- (90%) and physically- (86%) assaulted women were likely to recall the incident. Sexually-assaulted women had a significantly-higher mean for avoidance/numbness (p 0.051). About 41% of sexually-assaulted participants reported severe depression. Findings confirmed that sexual assault is more personal whilst physical assault is more interpersonal. If physically-assaulted women were removed from the perpetrators they recovered faster than sexually-assaulted women. Their stay with the perpetrators may perpetuate the violence. Conclusion: The need for counselling and support for the survivors of both traumas was recommended. All stakeholders should be educated to provide support to survivors of both traumas.   Agtergrond: Ten spyte daarvan dat daar intervensies beskikbaar is, bly geslagsgebaseerde geweld ‘n uitdaging in Suid-Afrika. Die versorging van die oorlewendes geweld is van kritieke belang om die oorlewendes se spoedige herstel te verseker. Doelwitte: Die doel was om die gevolge van trauma op die vroulike slagoffers van seksuele aanranding te vergelyk met die trauma wat die oorlewendes van fisiese aanranding ervaar het. Metode: ‘n Kwantitatiewe dwarssnit ontwerp is gebruik om 30 seksueel aangerande vroue en 30 fisiek aangerande vroue te vergelyk sover dit depressiesimptome, posttroumatiese stresversteuring en coping styl betref drie maande na die voorval plaasgevind het. Semi-gestruktureerde onderhoude is gevoer met die oorlewendes van beide soorte aanvalle, terwyl die Beck depressie-inventaris, die kontrolelys vir posttroumatiese stresversteuring en die bondige COPE-inventaris afgeneem is om kwantitatiewe data te bekom. Sowel parametriese as nie-parametriese statistiek is gebruik. Etiese vereistes is regdeur die navorsingsproses nagekom. Resultate: ‘n Aansienlik hoĂ«r persentasie seksueel aangerande vrouens het hulle gesin oor die voorval ingelig (p = 0.021). Die meeste seksueel (90%) en fisiek (86%) aangerande vrouens het die voorval onthou. Seksueel aangerande vrouens toon ‘n aansienlik hoĂ«r gemiddelde vir vermyding of gevoelloosheid (p 0.051). Sowat 41% van die seksueel aangerande deelnemers meld erge depressie. Die studie bevestig dat seksuele aanranding persoonliker is, terwyl fisieke aanranding meer interpersoonlik is. As fisiek aangerand vroue van die oortreders verwyder word, herstel hulle vinniger as die seksueel aangerande vroue. As hulle by die oortreders bly, kan die geweld voortduur. Gevolgtrekking: Die noodsaak aan berading en ondersteuning vir beide groepe oorlewendes word aanbeveel. Alle belanghebbendes moet opgevoed word om ondersteuning aan oorlewendes te bied
    corecore