ABSTRACT
Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.
Subject(s)
Camelids, New World , Immunoglobulin Heavy Chains , Mice, Transgenic , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus , Animals , Single-Domain Antibodies/genetics , Single-Domain Antibodies/immunology , Camelids, New World/immunology , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Mice , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Lectins, C-Type/metabolism , Lectins, C-Type/immunology , Lectins, C-Type/genetics , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Immunoglobulin E/immunology , Humans , Dependovirus/genetics , Dependovirus/immunology , Immunoglobulin G/immunology , COVID-19/immunology , B-Lymphocytes/immunologyABSTRACT
A Hanseníase é uma patologia infectocontagiosa e crônica, possui alto poder incapacitante e representa um grave problema para a saúde pública no Brasil. OBJETIVO: Traçar o perfil dos casos novos de hanseníase, classificados com o grau 2 de incapacidade física (GIF2) no momento do diagnóstico e descrever as principais incapacidades causadas pela doença. MÉTODOS: Estudo epidemiológico transversal, cujo levantamento de dados foi baseado nos prontuários, registros em Livros Ata nos arquivos do Ambulatório Municipal de Pneumologia e Dermatologia Sanitária de Guarapuava-PR e no Sistema de Informação de Agravos de Notificação do Ministério da Saúde. RESULTADOS: A presença do GIF2 foi mais frequente no sexo masculino, com cor de pele branca, baixa escolaridade, classificação operacional multibacilar, forma clínica virchowiana. As principais incapacidades encontradas foram lesões tróficas ou traumáticas em pés e garra em mãos. CONCLUSÃO: Há necessidade de intensificar as ações educativas para prevenção, contribuindo para o diagnóstico precoce da doença e evitando as incapacidades. (AU)
Leprosy was an infectious and chronic pathology, with high incapacitating power, and represents a serious problem for public health in Brazil. OBJECTIVE: To describe the profile of new cases of leprosy classified as grade 2 physical disability (G2D) at the time of diagnosis, and to describe the main disabilities caused by the disease. METHODS: Cross-sectional epidemiological study, whose data collection was based on medical records, records in books in the archives of the Municipal Ambulatory of Pneumology and Sanitary Dermatology of Guarapuava-PR, and in the Information System of Notifiable Ministry of Health Diseases. RESULTS: The presence of GIF2 is more frequent in maleswith white skin color, low level of education, multibacillary operational classification, virchowian clinical form. The main disabilities were trophic or traumatic lesions in the foot, and claw hands. CONCLUSION: It is necessary to enhance educational actions for prevention, contributing to the early diagnosis of the disease, and avoiding disabilities. (AU)
