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2.
Front Immunol ; 12: 728936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484239

RESUMO

The use of minimal peptide sets offers an appealing alternative for design of vaccines and T cell diagnostics compared to conventional whole protein approaches. T cell immunogenicity towards peptides is contingent on binding to human leukocyte antigen (HLA) molecules of the given individual. HLA is highly polymorphic, and each variant typically presents a different repertoire of peptides. This polymorphism combined with pathogen diversity challenges the rational selection of peptide sets with broad immunogenic potential and population coverage. Here we propose PopCover-2.0, a simple yet highly effective method, for resolving this challenge. The method takes as input a set of (predicted) CD8 and/or CD4 T cell epitopes with associated HLA restriction and pathogen strain annotation together with information on HLA allele frequencies, and identifies peptide sets with optimal pathogen and HLA (class I and II) coverage. PopCover-2.0 was benchmarked on historic data in the context of HIV and SARS-CoV-2. Further, the immunogenicity of the selected SARS-CoV-2 peptides was confirmed by experimentally validating the peptide pools for T cell responses in a panel of SARS-CoV-2 infected individuals. In summary, PopCover-2.0 is an effective method for rational selection of peptide subsets with broad HLA and pathogen coverage. The tool is available at https://services.healthtech.dtu.dk/service.php?PopCover-2.0.


Assuntos
Epitopos de Linfócito T/imunologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Peptídeos/imunologia , Alelos , Alergia e Imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Genótipo , Antígenos HLA/classificação , Humanos , Imunogenicidade da Vacina , Técnicas Imunológicas , Peptídeos/classificação , SARS-CoV-2/imunologia
7.
Am J Clin Dermatol ; 22(4): 443-455, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34076879

RESUMO

Dupilumab is the only biologic therapy currently approved in Europe and the United States for severe atopic dermatitis in patients 6 years of age or older. Off-label use is rationalized in younger children with severe atopic dermatitis. Decisions about vaccination for children on dupilumab are complex and depend on both the child's current treatment and the type of vaccination required. To achieve consensus on recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab, a review of the literature and a modified-Delphi process was conducted by a working group of 5 panelists with expertise in dermatology, immunology, infectious diseases and vaccination. Here, we provide seven recommendations for vaccination of pediatric patients with atopic dermatitis treated with or planning to start dupilumab. These recommendations serve to guide physicians' decisions about vaccination in children with atopic dermatitis treated with dupilumab. Furthermore, we highlight an unmet need for research to determine how significantly dupilumab affects cellular and humoral immune responses to vaccination with live attenuated and inactivated vaccines.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Conferências de Consenso como Assunto , Dermatite Atópica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Vacinação/normas , Alergia e Imunologia/normas , Criança , Técnica Delfos , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatologia/normas , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunogenicidade da Vacina , Índice de Gravidade de Doença , Vacinação/efeitos adversos
13.
Front Immunol ; 12: 647536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936065

RESUMO

The field of immunology is rapidly progressing toward a systems-level understanding of immunity to tackle complex infectious diseases, autoimmune conditions, cancer, and beyond. In the last couple of decades, advancements in data acquisition techniques have presented opportunities to explore untapped areas of immunological research. Broad initiatives are launched to disseminate the datasets siloed in the global, federated, or private repositories, facilitating interoperability across various research domains. Concurrently, the application of computational methods, such as network analysis, meta-analysis, and machine learning have propelled the field forward by providing insight into salient features that influence the immunological response, which was otherwise left unexplored. Here, we review the opportunities and challenges in democratizing datasets, repositories, and community-wide knowledge sharing tools. We present use cases for repurposing open-access immunology datasets with advanced machine learning applications and more.


Assuntos
Alergia e Imunologia , Biologia Computacional/métodos , Conjuntos de Dados como Assunto , Sistema Imunitário , Aprendizado de Máquina , Humanos , Metanálise como Assunto
14.
Allergy Asthma Proc ; 42(4): 301-309, 2021 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030767

RESUMO

Background: Most U.S. patient and health care provider surveys with regard to nasal allergy treatments were conducted before sublingual immunotherapy (SLIT)-tablets and allergy immunotherapy (AIT) shared decision-making tools were available. Objective: Patient and health care provider surveys with regard to current perceptions of nasal allergy burden, symptoms, and treatments were conducted to compare with previous surveys and provide insight into the use of SLIT-tablets and AIT shared decision-making tools. Methods: From November-December 2019, adults (N = 510) diagnosed with nasal allergies and health care providers (N = 304) who treated nasal allergies in the United States completed surveys with regard to nasal allergy management. Results: Of the patient respondents, 42% reported that their symptoms were only somewhat controlled and 48% had avoided activities because of their nasal allergies. In all, 38% were using only over-the-counter (OTC) medications for treatment, and 42%, 7%, and 8% had ever received subcutaneous immunotherapy (SCIT), sublingual allergy drops, or SLIT-tablets, respectively; 56% and 85% reported that they had never discussed SCIT or SLIT, respectively, with their health care provider. Of the health care provider respondents, 45%, 58%, and 20% were very likely to discuss OTC medications, SCIT, or SLIT, respectively. Allergists were more inclined to discuss SCIT with their patients than other health care providers (82% versus 33%, respectively). Most allergists (67%) and other health care providers (62%) reported that they did not use an AIT shared decision-making tool, primarily because of unawareness. Conclusion: The patients with nasal allergies continued to report inadequate symptom control and activity impairment. SLIT-tablets and AIT shared decision-making tools were underused. In the coronavirus disease 2019 era, social distancing may limit office visits, which impacts SCIT administration and prompts increased use of telemedicine and a possible advantage for at-home-administered SLIT-tablets over SCIT.


Assuntos
Alergia e Imunologia/tendências , COVID-19 , Tomada de Decisão Compartilhada , Técnicas de Apoio para a Decisão , Dessensibilização Imunológica/tendências , Medicamentos sem Prescrição/uso terapêutico , Padrões de Prática Médica/tendências , Rinite Alérgica/terapia , Telemedicina/tendências , Adolescente , Adulto , Idoso , Pesquisas sobre Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Distanciamento Físico , Prognóstico , Rinite Alérgica/diagnóstico , Imunoterapia Sublingual/tendências , Fatores de Tempo , Estados Unidos , Adulto Jovem
15.
J Biol Chem ; 296: 100745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33957119

RESUMO

Fifty years ago, the first landmark structures of antibodies heralded the dawn of structural immunology. Momentum then started to build toward understanding how antibodies could recognize the vast universe of potential antigens and how antibody-combining sites could be tailored to engage antigens with high specificity and affinity through recombination of germline genes (V, D, J) and somatic mutation. Equivalent groundbreaking structures in the cellular immune system appeared some 15 to 20 years later and illustrated how processed protein antigens in the form of peptides are presented by MHC molecules to T cell receptors. Structures of antigen receptors in the innate immune system then explained their inherent specificity for particular microbial antigens including lipids, carbohydrates, nucleic acids, small molecules, and specific proteins. These two sides of the immune system act immediately (innate) to particular microbial antigens or evolve (adaptive) to attain high specificity and affinity to a much wider range of antigens. We also include examples of other key receptors in the immune system (cytokine receptors) that regulate immunity and inflammation. Furthermore, these antigen receptors use a limited set of protein folds to accomplish their various immunological roles. The other main players are the antigens themselves. We focus on surface glycoproteins in enveloped viruses including SARS-CoV-2 that enable entry and egress into host cells and are targets for the antibody response. This review covers what we have learned over the past half century about the structural basis of the immune response to microbial pathogens and how that information can be utilized to design vaccines and therapeutics.


Assuntos
Imunidade Adaptativa , Anticorpos Antivirais/química , Antígenos Virais/química , Imunidade Inata , Receptores de Antígenos de Linfócitos T/química , Receptores de Citocinas/química , SARS-CoV-2/imunologia , Alergia e Imunologia/história , Animais , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Apresentação do Antígeno , Antígenos Virais/genética , Antígenos Virais/imunologia , COVID-19/imunologia , COVID-19/virologia , Cristalografia/história , Cristalografia/métodos , História do Século XX , História do Século XXI , Humanos , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia , SARS-CoV-2/patogenicidade , Recombinação V(D)J
19.
Immunology ; 163(4): 431-435, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34002402

RESUMO

The pandemic has brought challenges to teaching lab and research skills. Here Nigel Francis and colleagues explore the diverse approaches taken to replace lab-based immunology teaching, explain how networks of educators have driven this innovation and discuss the importance of retaining best practice into the future.


Assuntos
Alergia e Imunologia/educação , Pesquisa Biomédica/educação , COVID-19 , Instrução por Computador , Educação à Distância , Laboratórios , Estudantes , Ensino , Currículo , Humanos
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