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1.
Protein Eng Des Sel ; 22(3): 189-98, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19054791

RESUMO

M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.


Assuntos
Anticorpos Monoclonais/imunologia , Região Variável de Imunoglobulina/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Proteínas da Matriz Viral/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Especificidade de Anticorpos , Embrião de Galinha , Cães , Citometria de Fluxo , Humanos , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/metabolismo , Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/metabolismo , Camundongos , Dados de Sequência Molecular , Testes de Neutralização , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Ensaio de Placa Viral
2.
Vet Immunol Immunopathol ; 123(3-4): 305-13, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18394715

RESUMO

It has been established that maternal leukocytes, conditioned by the mammary environment, cross the neonatal gut and circulate in the newborn calf. However, the impact of these cells on the development of neonatal immunity remains to be determined. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal adaptive immunity by examining the expression of surface markers on neonatal lymphocytes. At birth, neonatal calves were fed whole colostrum, or colostrum that had the maternal cells removed (cell-free colostrum), from their respective dams. Peripheral blood samples were collected at regular intervals over the first 4 weeks of life and lymphocytes were evaluated for surface expression of cellular markers. The results of these studies demonstrated that calves receiving whole colostrum had fewer CD11a positive lymphocytes in circulation during the first 2 weeks of life and this marker was expressed at a lower density than calves receiving cell-free colostrum. In addition, calves receiving whole colostrum also had a higher percentage of lymphocytes expressing the activation markers CD25 and CD26 by 7 days after birth. During the first week of life, lymphocytes from calves receiving whole colostrum had a higher density of MHC class I expression on their surfaces than cells from calves receiving cell-free colostrum. In general, these results indicate that transfer of maternal cells with colostrum allows for more rapid development of lymphocytes and maternal cells appeared to enhance their activation.


Assuntos
Bovinos/imunologia , Colostro/imunologia , Imunidade Materno-Adquirida/imunologia , Imunoglobulina G/sangue , Leucócitos Mononucleares/imunologia , Linfócitos/imunologia , Animais , Animais Recém-Nascidos , Antígenos CD/sangue , Antígenos CD/imunologia , Colostro/citologia , Feminino , Citometria de Fluxo/veterinária , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/sangue , Antígenos de Histocompatibilidade Classe II/imunologia , Imunofenotipagem/estatística & dados numéricos , Gravidez
3.
Vet Immunol Immunopathol ; 123(3-4): 186-96, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18321594

RESUMO

Although it has been established that maternal leukocytes traffic from colostrum into the neonatal circulation, the effects of these cells on neonatal immunity are only beginning to be understood. This study examined the effects of maternal colostral leukocytes on development and maturation of neonatal antigen presenting cells. At birth, groups of neonatal calves received whole or cell-free colostrum (CFC) from their respective dams. Peripheral blood samples were obtained over the first 4 weeks of life, and expression of surface markers associated with cellular activation and physiological stress were monitored on monocyte lineage cells. Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a, CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves receiving cell-free colostrum had an elevated number of monocytes in the peripheral blood during the first 2 weeks of life, however, these cells expressed lower levels of expression of CD25 and MHC class I compared to calves receiving whole colostrum. The most significant differences in marker expression occurred within the first 7 days of life.


Assuntos
Bovinos/imunologia , Colostro/imunologia , Leucócitos Mononucleares/imunologia , Animais , Animais Recém-Nascidos , Apresentação de Antígeno , Antígeno CD11a/biossíntese , Antígeno CD11a/sangue , Antígeno CD11c/biossíntese , Antígeno CD11c/sangue , Bovinos/sangue , Linhagem da Célula/imunologia , Colostro/citologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Citometria de Fluxo/veterinária , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Imunoglobulina G/sangue , Imunofenotipagem/veterinária , Receptores de Lipopolissacarídeos/biossíntese , Receptores de Lipopolissacarídeos/sangue , Óxido Nítrico/biossíntese , Óxido Nítrico/sangue
4.
Nucleic Acids Res ; 35(Database issue): D401-6, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17142235

RESUMO

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.


Assuntos
Bioterrorismo , Bases de Dados Genéticas , Proteobactérias/genética , Vírus de RNA/genética , Genômica , Internet , Proteobactérias/metabolismo , Proteobactérias/patogenicidade , Proteômica , Vírus de RNA/metabolismo , Vírus de RNA/patogenicidade , Integração de Sistemas , Interface Usuário-Computador
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