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1.
Biochemistry (Mosc) ; 89(5): 862-871, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38880647

RESUMO

Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Antígenos Virais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Neutralizantes/imunologia
2.
Indian J Med Microbiol ; 50: 100615, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38782260

RESUMO

BACKGROUND: Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of "future" variants in the context of such heterogeneous exposure has not been studied. METHODS: We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework. RESULTS: Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both 'High S' and 'Low S' of Delta and Omicron periods were closely related to "future" subvariants by Antigenic Cartography. Sera from different S groups clustered together with 'Low S' interspersed between 'High S' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies. CONCLUSIONS: Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to "future" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the 'Low S' antibody demonstrates similar binding.

3.
Virol J ; 21(1): 70, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515117

RESUMO

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.


Assuntos
Vacina BNT162 , COVID-19 , Humanos , Anticorpos Amplamente Neutralizantes , SARS-CoV-2/genética , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Vacinação , Anticorpos Antivirais
4.
RECIIS (Online) ; 18(1)jan.-mar. 2024.
Artigo em Português | LILACS, Coleciona SUS | ID: biblio-1553055

RESUMO

O objetivo do presente artigo foi realizar uma cartografia de um Consultório na Rua, durante o período da pandemia de covid-19. A cartografia foi produzida por uma vivência no consultório de um município de grande porte no sul do Brasil, de agosto de 2021 a janeiro de 2022. Foi perceptível que a locomoção e o funcionamento do serviço reconhecem outros territórios das Pessoas em Situação de Rua, muitas vezes não percebidos por outros pontos do Sistema Único de Saúde. Foram encontradas tanto as barreiras já estabelecidas historicamente quanto as emergentes da pandemia. Foi vivenciado que a esta população não utiliza o território do modo que a cidade racionalizada planeja, sendo, portanto, singular. O reconhecimento do serviço, aliado à compreensão de como as Pessoas em Situação de Rua vivem no território urbano, em cada realidade, mostrou-se essencial para a produção de cuidado.


The objective of this article was to conduct a cartographic study of a street clinic during the covid-19 pandemic. The cartography was based on an experiential approach in a street clinic located in a major city in southern Brazil, between August 2021 and January 2022. It became evident that the flows and operation of the service acknowledged the alternative territories inhabited by the homeless population, often overlooked by other parts of Brazil's Unified Health System. Both historically established barriers and those emerging from the pandemic were encountered. It was observed that the homeless population does not conform to rationalized urban plans, displaying unique patterns of engagement with the urban territory. Recognizing the significance of the service, coupled with a comprehensive understanding of the unique living conditions of homeless individuals, proved indispensable for the provision of effective care.


El objetivo de este artículo fue realizar una cartografía de un Consultorio en la Calle durante el período de la pandemia del covid-19. La cartografía fue producida por una experiencia en un Consultorio en la Calle en una gran ciudad del sur de Brasil, de agosto de 2021 a enero de 2022. Se pudo observar que la locomoción y operación del servicio reconocen otros territorios habitados por personas en situación de calle, a menudo no percibidos por otros puntos del Sistema Único de Salud. Se encontraron barreras, tanto históricamente establecidas como emergentes debido a la pandemia. Se constató que la población en situación de calle no utiliza el territorio de la forma planificada por la ciudad racionalizada. El reconocimiento del servicio, junto con la comprensión de cómo viven las personas en situación de calle en el territorio urbano en cada realidad, se mostró fundamental para la producción del cuidado.


Assuntos
Humanos , Política Pública , Pessoas Mal Alojadas , COVID-19 , Qualidade Habitacional , Vulnerabilidade Social , População
5.
bioRxiv ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38370637

RESUMO

Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.

6.
Skin Res Technol ; 30(2): e13623, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38385854

RESUMO

BACKGROUND: Facial dark spots remain a significant challenge for the cosmetic industry, in terms of providing effective treatment. Using Line-field Confocal Optical Coherence Tomography (LC-OCT), we investigated the internal structural features of photo-aging spot areas and evaluated the efficacy of a skin-brightening cosmetic product. MATERIALS AND METHODS: Twenty-six Asian female volunteers, aged between 29 and 65 years, applied a cosmetic product on their entire face twice a day for 2 months. LC-OCT was used to evaluate the dermal-epidermal junction (DEJ) undulation and the volume density of melanin in the epidermis at D0 and D56. Skin brightening and redness were also assessed by photography (SkinCam). RESULTS: Using LC-OCT technology, various microscopic dark spot morphologies, spanning from minimally deformed DEJ to complex DEJ patterns, were identified. Dark spots characterized by slight deformities in the DEJ were predominantly observed in the youngest age group, while older volunteers displayed a wavier pattern. Furthermore, a total of 44 spots were monitored to evaluate the brightening product efficacy. A statistically significant reduction in melanin volumetric density of 7.3% in the spots and 12.3% in their surrounding area was observed after 56 days of product application. In line with these results, an analysis of color parameters using SkinCam reveals a significant increase in brightening and decrease in redness in both pigmented spots and the surrounding skin following application. CONCLUSIONS: LC-OCT proves to be a valuable tool for in-depth dark spots characterization and assessment of skin brightening products, enabling various applications in the field of dermatological sciences.


Assuntos
Melaninas , Transtornos da Pigmentação , Feminino , Humanos , Recém-Nascido , Tomografia de Coerência Óptica , Pele/diagnóstico por imagem , Epiderme/diagnóstico por imagem
7.
Interface (Botucatu, Online) ; 28: e230342, 2024. graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1558198

RESUMO

O estudo objetivou mapear as estratégias utilizadas para o trabalho colaborativo em equipes de Saúde da Família (eSF) inseridas na Atenção Primária à Saúde (APS), em um município do norte de Minas. Trata-se de um estudo qualitativo, com a proposta metodológica da Cartografia. Os dados foram produzidos em quatro eSF por meio de observação participante, questionário de identificação, diário cartográfico, entrevista semiestruturada individual e grupo focal. A análise do discurso e o rastreio cartográfico possibilitaram a construção de duas categorias temáticas e um mapa cartográfico. Alcançou-se que as estratégias, consideradas linhas de fuga, permitem transformações existenciais no trabalho em equipe, pois originam nascentes em solos cristalizados, pensamentos problematizadores, subjetividade e interações disciplinares. Concluiu-se que as linhas duras não devem ser eliminadas do trabalho em equipe, pois coexistem nessa realidade, e o que importa é como são vivenciadas nas relações.


El objetivo del estudio fue mapear las estrategias utilizadas para el trabajo colaborativo en equipos de Salud de la Familia (eSF), inseridas en la Atención Primaria de la Salud, en un municipio del Norte de Minas Gerais. Se trata de un estudio cualitativo, con la propuesta metodológica de la Cartografía. Los datos se produjeron en cuatro eSF, por medio de observación participativa, cuestionario de identificación, diario cartográfico, entrevista semiestructurada individual y grupo focal. El análisis del discurso y el rastreo cartográfico posibilitaron la construcción de dos categorías temáticas y un mapa cartográfico. Se vio que las estrategias, consideradas líneas de fuga, permiten transformaciones en el trabajo en equipo, puesto que originan manantiales en suelos cristalizados, pensamientos problematizadores, subjetividad e interacciones disciplinarias. Se concluyó que las líneas duras no deben eliminarse del trabajo en equipo, puesto que coexisten en esta realidad y lo que importa es cómo se experimentan en las relaciones.


The study aimed to map the strategies used for collaborative work in Family Health Teams (FHT), inserted in Primary Health Care, in a municipality in the North of Minas. This is a qualitative study, with the methodological proposal of Cartography. Data were produced in four FHT, through participant observation, identification questionnaire, cartographic diary, semi-structured individual interview and focus group. Discourse analysis and mapping screening enabled the construction of two thematic categories and a cartographic map. It was reached that the strategies, considered lines of flight, allow existential transformations in teamwork, since they originate springs in crystallized soils, problematizing thoughts, subjectivity, and disciplinary interactions. It was concluded that hard lines should not be eliminated from teamwork, for they coexist in this reality, and what matters is how they are experienced in relationships.

8.
Data Brief ; 51: 109689, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38099148

RESUMO

The objective of this document is to introduce the datasets and the methods for accessing them, derived from the article "Social, commercial, and economic diversity. Poverty and expectations among street vendors in Florencia, Caquetá, Colombia." These datasets aim to provide insights into the conditions and characteristics of street vending in Colombia. The data collection process involved both mapping and personal surveys conducted on 190 street vendors. Additionally, practical recommendations are provided for tailoring the implementation of each survey instrument based on the specific attributes of the study's target demographic. The collected data holds the potential for comparative and longitudinal analyses, not only within different Colombian cities but also in cities worldwide facing similar circumstances to those of intermediate cities like Florencia. These datasets offer a valuable resource for understanding the dynamics of street vending and its implications, fostering more comprehensive research and informed policymaking.

9.
Psicol. rev ; 32(2): 322-343, 31/12/2023.
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1552099

RESUMO

O objetivo deste trabalho foi discutir acerca da utilização de um dispositivo de pesquisa: o caderno digital itinerante, a partir do qual foi possível promover a construção conjunta de uma pesquisa, partindo do método cartográfico. A pesquisa de campo que deu origem a esta reflexão metodológica teve por objetivo principal cartografar experiências sapatão na cidade, por meio da construção conjunta de um caderno digital itinerante no qual as participantes, juntamente com a pesquisadora, escreviam sobre suas experiências como mulheres lésbicas e/ou pessoas que se reconheciam enquanto sapatão. Tendo como um dos instrumentos a análise do diário de campo, produzido durante a pesquisa, foi possível discutir em profundidade o enfoque metodológico adotado e questionar a dicotomia pesquisadora-objeto, provocando algumas reflexões acerca da temática da participação e do desenvolvimento de pesquisas on-line, sobretudo no período pandêmico. Por fim, apostar na cartografia enquanto método de pesquisa com e não sobre permitiu a produção de uma pesquisadora sapatão que pudesse se ocupar da escuta, lendo sobre diferentes processos de subjetivação e, com isso, produzindo outros sentidos para seu objeto de pesquisa. (AU)


The aim of this study was to discuss the use of a research tool: the itinerant digital notebook, which facilitated the collaborative construction of research based on the cartographic method. The field research that gave rise to this methodological reflection aimed to map dyke experiences in the city through the collaborative construction of an itinerant digital notebook. In this note-book, participants, alongside the researcher, wrote about their experiences as lesbian women and/or individuals who identified as dykes. Using the analysis of the field diary produced during the research as one of the instruments, it was possible to deeply discuss the adopted methodological approach and question the researcher-object dichotomy, prompting reflections on the theme of participation and the development of online research, especially during the pandemic period. Ultimately, embracing cartography as a research method with, not on, participants allowed the production of a dyke researcher who could engage in listening, reading about different processes of subjectivation, and thereby generating alternative meanings for her object of study. (AU)


El objetivo de este trabajo fue discutir el uso de un dispositivo de investigación: el cuaderno digital itinerante, a partir del cual fue posible promover la cons-trucción conjunta de una investigación, a partir del método cartográfico. La investigación de campo que dio origen a esta reflexión metodológica tuvo como objetivo principal mapear las experiencias lesbianas en la ciudad, a través de la construcción conjunta de un cuaderno digital itinerante en el que las parti-cipantes, junto con la investigadora, escribieron sobre sus experiencias como lesbianas y/o personas que se reconocían como bolleras/camioneras. Teniendo como uno de los instrumentos el análisis del diario de campo producido durante la investigación, fue posible discutir en profundidad el abordaje metodológico adoptado y cuestionar la dicotomía investigadora-objeto, provocando algunas reflexiones sobre el tema de la participación y el desarrollo de investigación, especialmente en el período de pandemia. Finalmente, apostar por la carto-grafía como método de investigación con participantes y no sobre las partici-pantes permitió producir una investigadora lesbiana que podía ocuparse de escuchar, leer sobre diferentes procesos de subjetivación y, con eso, producir otros significados para su objeto de investigación. (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Pesquisa/instrumentação , Metodologia como Assunto , Psicologia Social , Relações Pesquisador-Sujeito , Minorias Sexuais e de Gênero , Internet das Coisas , COVID-19
10.
Viruses ; 15(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38005926

RESUMO

The H5 subtype highly pathogenic avian influenza viruses bearing the clade 2.3.4.4 HA gene have been pervasive among domestic poultry and wild birds worldwide since 2014, presenting substantial risks to human and animal health. Continued circulation of clade 2.3.4.4 viruses has resulted in the emergence of eight subclades (2.3.4.4a-h) and multiple distinct antigenic groups. However, the key antigenic substitutions responsible for the antigenic change of these viruses remain unknown. In this study, we analyzed the HA gene sequences of 5713 clade 2.3.4.4 viruses obtained from a public database and found that 23 amino acid residues were highly variable among these strains. We then generated a series of single-amino-acid mutants based on the H5-Re8 (a vaccine seed virus) background and tested their reactivity with a panel of eight monoclonal antibodies (mAbs). Six mutants bearing amino acid substitutions at positions 120, 126, 141, 156, 185, or 189 (H5 numbering) led to reduced or lost reactivity to these mAbs. Further antigenic cartography analysis revealed that the amino acid residues at positions 126, 156, and 189 acted as immunodominant epitopes of H5 viruses. Collectively, our findings offer valuable guidance for the surveillance and early detection of emerging antigenic variants.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Animais , Humanos , Hemaglutininas , Virus da Influenza A Subtipo H5N1/genética , Aminoácidos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A/genética , Anticorpos Monoclonais
11.
Rev. polis psique ; 13(2): 6-28, 2023-11-13. ilus
Artigo em Português | LILACS, Index Psicologia - Periódicos | ID: biblio-1517838

RESUMO

Esse trabalho decorre da produção da pesquisa "Potências clínicas nos corpos em criação nas experimentações artísticas do programa TOCCA" realizada durante os anos de 2018 e 2021. O artigo se volta a mostrar a análise cartográfica de um dos grupos observados e os processos de constituição de corpos dançarinos e de uma obra em dança. Compreendeu-se que o entrelaçamento dos conhecimentos da terapia ocupacional e das artes da cena pode vir a criar saberes transversais, desde as práticas de educação somática, que fortalecem e ampliam ambos os campos em suas potências éticas, estéticas e políticas. Bem como, podem instaurar um dispositivo poético clínico para a produção do comum. (AU)


This work stems from the production of the research "Clinical potencies in bodies under creation in the artistic experimentations of the TOCCA program" carried out during the years 2018 and 2021. The article returns to show the analysis of one of the observed groups and the processes of constitution of dancing bodies and a work in dance. It was understood that the interweaving of knowledge from occupational therapy and performing arts can create transversal knowledge, from somatic education practices, which strengthen and expand both fields in their ethical, aesthetic and political powers. As well as, they can establish a clinical poetic device for the production of the common. (AU)


Este trabajo surge de la producción de la investigación "Potencias clínicas en cuerpos en creación en las experimentaciones artísticas del programa TOCCA" realizada durante los años 2018 y 2021. El artículo vuelve a mostrar el análisis de uno de los grupos observados y los procesos de constitución de cuerpos danzantes y un trabajo en danza. Se entendió que el entrecruzamiento de los saberes de la terapia ocupacional y las artes escénicas puede generar conocimientos transversales, a partir de prácticas de educación somática, que fortalezcan y amplíen ambos campos en sus poderes éticos, estéticos y políticos. Así como, pueden establecer un dispositivo poético clínico para la producción de lo común. (AU)


Assuntos
Humanos , Masculino , Feminino , Terapia Ocupacional , Criatividade , Dança/psicologia
12.
Sante Publique ; 35(3): 235-250, 2023 10 17.
Artigo em Francês | MEDLINE | ID: mdl-37848371

RESUMO

Introduction: In the Centre-Val de Loire region, the demography of specialty care is characterized by a strong deficit and many territorial inequalities that lead to significant difficulties in accessing care. The study has being conducted at the level of the Professional Territorial Health Communities (CPTS) which structuring the region, which is the ideal framework for implementing public health actions resulting from this study. Purpose of research: The aim of this study was to objectify these difficulties and their geography, based on the calculation of the comparative consumption index (CCI), in order to measure the differences between expected consumption and observed consumption, and to quantify the number of "missing" doctors to meet the needs of the population. Results: The study shows a deficit in care-seeking for specialty care, in particular an incompatibility between care needs and care offers in the living environment, as well as strong territorial inequalities, with marked differences between private consumption and hospital consumption. The region experiences a deficit of 25% of liberal medical specialists in order to meet the needs of its population. Conclusions: Accessibility to care is not only defined by the proximity of doctors, and their density; the proximity of areas of activity being a factor associated with better access to health care. This study also makes it possible to identify priority areas of action, specialty by specialty, to strengthen access to specialty care, and propose a fairer distribution of the care offer, in particular through interns' internships, and the coordinated and territorial organization of specialist doctors.


Introduction: En région Centre-Val de Loire, l'offre de soins de second recours se caractérise par une démographie déficitaire et par de fortes inégalités territoriales, entraînant d'importantes difficultés d'accès aux soins. L'étude a été menée à l'échelle des communautés professionnelles territoriales de santé (CPTS) maillant la région, cadre idéal pour concrétiser des actions de santé publique. But de l'étude: Le but de cette étude était d'objectiver ces difficultés et leur géographie, sur la base du calcul de l'indice comparatif de consommation (ICC), afin de mesurer les écarts entre la consommation attendue et la consommation observée, et de quantifier le nombre de médecins nécessaires pour répondre aux besoins de la population, et qui sont donc actuellement « manquants ¼. Résultats: On observe un sous-recours aux soins de spécialité, notamment une inadéquation entre les besoins et l'offre de soins sur les lieux de vie, ainsi que de fortes inégalités territoriales, avec des différences marquées entre le recours libéral et le recours aux actes et consultations externes en secteur hospitalier. La région connaîtrait un déficit de 25 % de médecins spécialistes libéraux pour répondre aux besoins de sa population. Conclusions: L'accessibilité aux soins ne se résume pas à la proximité des soignants ni à leur densité, la proximité de zones d'activité étant un facteur associé à un meilleur recours aux soins. Cette étude permet d'identifier des zones d'action prioritaire par spécialité, pour renforcer l'accès au second recours et construire une plus juste répartition de l'offre, notamment par le déploiement de stages d'internes et l'organisation coordonnée et territoriale des médecins spécialistes hors médecine générale.


Assuntos
Atenção à Saúde , Médicos , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Encaminhamento e Consulta , Instalações de Saúde
13.
J Virol ; 97(10): e0074323, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37800947

RESUMO

IMPORTANCE: Determining the relevant amino acids involved in antigenic drift on the surface protein hemagglutinin (HA) is critical to understand influenza virus evolution and efficient assessment of vaccine strains relative to current circulating strains. We used antigenic cartography to generate an antigenic map of the H9 hemagglutinin (HA) using sera produced in one of the most relevant minor poultry species, Japanese quail. Key antigenic positions were identified and tested to confirm their impact on the antigenic profile. This work provides a better understanding of the antigenic diversity of the H9 HA as it relates to reactivity to quail sera and will facilitate a rational approach for selecting more efficacious vaccines against poultry-origin H9 influenza viruses in minor poultry species.


Assuntos
Deriva e Deslocamento Antigênicos , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Animais , Coturnix , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/virologia , Aves Domésticas
14.
Cell Rep Methods ; 3(8): 100566, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37671022

RESUMO

The increasing use of monoclonal antibodies (mAbs) in biology and medicine necessitates efficient methods for characterizing their binding epitopes. Here, we developed a high-throughput antibody footprinting method based on binding profiles. We used an antigen microarray to profile 23 human anti-influenza hemagglutinin (HA) mAbs using HA proteins of 43 human influenza strains isolated between 1918 and 2018. We showed that the mAb's binding profile can be used to characterize its influenza subtype specificity, binding region, and binding site. We present mAb-Patch-an epitope prediction method that is based on a mAb's binding profile and the 3D structure of its antigen. mAb-Patch was evaluated using four mAbs with known solved mAb-HA structures. mAb-Patch identifies over 67% of the true epitope when considering only 50-60 positions along the antigen. Our work provides proof of concept for utilizing antibody binding profiles to screen large panels of mAbs and to down-select antibodies for further functional studies.


Assuntos
Influenza Humana , Medicina , Humanos , Anticorpos Monoclonais , Epitopos , Sítios de Ligação
15.
Cell Rep Methods ; 3(10): 100597, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37751739

RESUMO

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues.


Assuntos
Cistos , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Epitélio , Células Epiteliais
16.
Cell Host Microbe ; 31(8): 1301-1316.e8, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37527659

RESUMO

Current COVID-19 vaccines are highly effective against symptomatic disease, but repeated booster doses using vaccines based on the ancestral strain offer limited additional protection against SARS-CoV-2 variants of concern (VOCs). To address this, we used antigenic distance to in silico select optimized booster vaccine seed strains effective against both current and future VOCs. Our model suggests that a SARS-CoV-1-based booster vaccine has the potential to cover a broader range of VOCs. Candidate vaccines including the spike protein from ancestral SARS-CoV-2, Delta, Omicron (BA.1), SARS-CoV-1, or MERS-CoV were experimentally evaluated in mice following two doses of the BNT162b2 vaccine. The SARS-CoV-1-based booster vaccine outperformed other candidates in terms of neutralizing antibody breadth and duration, as well as protective activity against Omicron (BA.2) challenge. This study suggests a unique strategy for selecting booster vaccines based on antigenic distance, which may be useful in designing future booster vaccines as new SARS-CoV-2 variants emerge.


Assuntos
COVID-19 , Animais , Humanos , Camundongos , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinas contra COVID-19 , Vacina BNT162 , Anticorpos Neutralizantes , Anticorpos Antivirais
17.
Skelet Muscle ; 13(1): 14, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612778

RESUMO

Histological analysis of skeletal muscle is of major interest for understanding its behavior in different pathophysiological conditions, such as the response to different environments or myopathies. In this context, many software programs have been developed to perform automated high-content analysis. We created MuscleJ, a macro that runs in ImageJ/Fiji on batches of images. MuscleJ is a multianalysis tool that initially allows the analysis of muscle fibers, capillaries, and satellite cells. Since its creation, it has been used in many studies, and we have further developed the software and added new features, which are presented in this article. We converted the macro into a Java-language plugin with an improved user interface. MuscleJ2 provides quantitative analysis of fibrosis, vascularization, and cell phenotype in whole muscle sections. It also performs analysis of the peri-myonuclei, the individual capillaries, and any staining in the muscle fibers, providing accurate quantification within regional sublocalizations of the fiber. A multicartography option allows users to visualize multiple results simultaneously. The plugin is freely available to the muscle science community.


Assuntos
Músculo Esquelético , Células Satélites de Músculo Esquelético , Imunofluorescência , Fibras Musculares Esqueléticas , Software
18.
mBio ; 14(5): e0048823, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37565755

RESUMO

IMPORTANCE: A/H7 avian influenza viruses cause outbreaks in poultry globally, resulting in outbreaks with significant socio-economical impact and zoonotic risks. Occasionally, poultry vaccination programs have been implemented to reduce the burden of these viruses, which might result in an increased immune pressure accelerating antigenic evolution. In fact, evidence for antigenic diversification of A/H7 influenza viruses exists, posing challenges to pandemic preparedness and the design of vaccination strategies efficacious against drifted variants. Here, we performed a comprehensive analysis of the global antigenic diversity of A/H7 influenza viruses and identified the main substitutions in the hemagglutinin responsible for antigenic evolution in A/H7N9 viruses isolated between 2013 and 2019. The A/H7 antigenic map and knowledge of the molecular determinants of their antigenic evolution add value to A/H7 influenza virus surveillance programs, the design of vaccines and vaccination strategies, and pandemic preparedness.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária , Influenza Humana , Animais , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Hemaglutininas , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Variação Antigênica , Surtos de Doenças , Aves Domésticas , Influenza Aviária/epidemiologia , Influenza Aviária/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle
19.
Int J Mol Sci ; 24(13)2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37445671

RESUMO

The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.


Assuntos
Vacina BNT162 , COVID-19 , Humanos , Imunização Secundária , SARS-CoV-2/genética , COVID-19/prevenção & controle , Vacinação , Anticorpos Antivirais , Anticorpos Neutralizantes
20.
Viruses ; 15(7)2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37515180

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting. We investigated the prevalence of SARS-CoV-2 variant infections in domestic and community cats in the city of Pittsburgh (n = 272). While no cats tested positive for SARS-CoV-2 viral RNA, 35 cats (12.86%) tested SARS-CoV-2-antibody-positive. Further, we compared a cat-specific experimental lateral flow assay (eLFA) and species-agnostic surrogate virus neutralization assay (sVNT) for SARS-CoV-2 antibody detection in cats (n = 71). The eLFA demonstrated 100% specificity compared to sVNT. The eLFA also showed 100% sensitivity for sera with >90% inhibition and 63.63% sensitivity for sera with 40-89% inhibition in sVNT. Using a variant-specific pseudovirus neutralization assay (pVNT) and antigen cartography, we found the presence of antibodies to pre-Omicron and Omicron SARS-CoV-2 variants. Hence, this approach proves valuable in identifying cat exposure to different SARS-CoV-2 variants. Our results highlight the continued exposure of cats to SARS-CoV-2 and warrant coordinated surveillance efforts.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/veterinária , Pennsylvania , Prevalência , Anticorpos Antivirais , RNA , Anticorpos Neutralizantes , Mamíferos
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