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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 934-940, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33148389

RESUMO

Objective To prepare and preliminarily identify anti-mouse CD226 monoclonal antibodies (mAbs) using CD226 knockout (CD226 KO) mice as immunized animals. Methods Animals were immunized by recombinant mouse CD226 protein expressed by eukaryotic cells. Anti-mouse CD226 mAbs were prepared by conventional B-cell hybridoma technology. The application of the generated mAbs for flow cytometry and Western blotting was tested. A sandwich ELISA system was established for the detection of soluble CD226 in mice. And the concentrations of plasma soluble CD226 was determined by this sandwich ELISA system in an LPS-induced sepsis mouse model. Results Two hybridoma cell lines secreting mouse anti-mouse CD226 mAbs were successfully prepared. The clones were named mA1.1 and mA1.3, respectively. The antibody subclasses were both IgG1, and the light chains were κ. The obtained mAbs could be applied for flow cytometry to detect exogenous transfected CD226 on the cell surface and natural CD226 on the mouse platelet membrane. In Western blot assay, the mAb could bind to lymphocyte membrane proteins with a relative molecular mass (Mr) of 67 000 that was consistent with the Mr of CD226. In the sandwich ELISA system, the purified mAbs of mA1.3 were coated on ELISA plates as capture antibody, and the mAbs of mA1.1 were labeled with horseradish peroxidase or biotin as detection antibody. The detection sensitivities were 3.0 and 0.25 ng/mL, respectively. The concentration of plasma soluble CD226 of the septic mice was lower than that of the normal mice in the control group. Conclusion The mouse mAbs for identifying mouse CD226 have been prepared successfully and can be applied in various detection techniques.


Assuntos
Anticorpos Monoclonais/biossíntese , Antígenos de Diferenciação de Linfócitos T/imunologia , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Hibridomas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Sepse
3.
Arch Virol ; 165(12): 2789-2798, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32970278

RESUMO

Chickpea chlorotic dwarf virus (CpCDV, genus Mastrevirus), has a wide host range and geographic distribution in many parts of the world, and it is one of the most important legume-infecting viruses. Detection of CpCDV-infected plants in the field and evaluation of viral resistance of plant cultivars are possible by conducting serological assays. Here, development and characterization of a specific recombinant monoclonal antibody for CpCDV as a diagnostic tool are described. For this purpose, the coat protein of CpCDV was expressed in Escherichia coli strain Rosetta (DE3) and used to screen a Tomlinson phage display antibody library to select a specific single-chain variable fragment (scFv). In each round of biopanning, the affinity of the phage for CpCDV-CP was tested by enzyme-linked immunosorbent assay (ELISA). The results showed that the specificity of the eluted phages increased after each round of panning. Testing of individual clones by ELISA showed that five clones of the monoclonal phage were more strongly reactive against CpCDV than the other clones. All selected positive clones contained the same sequence. The phage-displayed scFv antibody, which was named CpCDV-scFvB9, did not bind to other tested plant pathogens and showed high sensitivity in the detection of CpCDV. A Western blot assay demonstrated that CpCDV-scFvB9 reacted with the recombinant coat protein of CpCDV. Finally, the interaction CpCDV-scFvB9 and CpCDV-CP was analyzed in a molecular docking experiment. This is the first report on production of an scFv antibody against CpCDV, which could be useful for immunological detection of the virus.


Assuntos
Especificidade de Anticorpos , Cicer/virologia , Geminiviridae/isolamento & purificação , Doenças das Plantas/virologia , Anticorpos de Cadeia Única/biossíntese , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/isolamento & purificação , Bacteriófagos/genética , Técnicas de Visualização da Superfície Celular , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Geminiviridae/genética , Simulação de Acoplamento Molecular , Filogenia , Análise de Sequência de DNA , Anticorpos de Cadeia Única/isolamento & purificação
4.
Signal Transduct Target Ther ; 5(1): 212, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963228

RESUMO

The outbreaks of severe acute respiratory syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV and SARS-CoV-2, respectively, have posed severe threats to global public health and the economy. Treatment and prevention of these viral diseases call for the research and development of human neutralizing monoclonal antibodies (NMAbs). Scientists have screened neutralizing antibodies using the virus receptor-binding domain (RBD) as an antigen, indicating that RBD contains multiple conformational neutralizing epitopes, which are the main structural domains for inducing neutralizing antibodies and T-cell immune responses. This review summarizes the structure and function of RBD and RBD-specific NMAbs against SARS-CoV and SARS-CoV-2 currently under development.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Epitopos/química , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Modelos Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Secundária de Proteína , Receptores Virais/química , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vírion/imunologia , Vírion/ultraestrutura
5.
J Biosci Bioeng ; 130(5): 525-532, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32800439

RESUMO

Chinese hamster ovary (CHO) cells are used as host cells for biopharmaceutical production, including monoclonal antibodies (mAbs). Arresting the cell cycle with chemical compounds is an effective approach to improve biopharmaceutical productivity. In a previous study, potential new cell cycle-arresting compounds were screened from marine-derived microorganism culture extracts, and it was suggested that staurosporine might improve mAb productivity in CHO cells via cell cycle arrest. The purpose of this study was to demonstrate the effectiveness of staurosporine as a cell-cycle arresting compound to improve mAb productivity. The optimal staurosporine concentration range was initially investigated using batch cultures. Thereafter, the effects on the culture profile and mAb productivity were evaluated using fed-batch cultures. Staurosporine at concentrations ≥10 nM induced cell death, but at concentrations ≤5 nM did not. In the range of 2-4 nM, cell growth was inhibited, whereas the specific production rate (Qp) and cell longevity were improved in a dose-dependent manner. The Qp and maximum mAb concentration with 4 nM staurosporine improved by 36.3 and 5.2%, respectively, compared to those with control conditions. Cell viability post-culture without staurosporine was 40.0 ± 0.3%, whereas with 4 nM staurosporine, it was 90.1 ± 1.0%. Flow cytometric analysis indicated cell-cycle arrest at the G1/G0 phase with 4 nM staurosporine addition. The present study highlighted the efficacy of staurosporine in improving mAb production by causing cell-cycle arrest. Further research into staurosporine analogs and how to use them will lead to development of more effective industrial production technologies of biopharmaceuticals.


Assuntos
Anticorpos Monoclonais/biossíntese , Proteínas Recombinantes/biossíntese , Estaurosporina/farmacologia , Animais , Técnicas de Cultura Celular por Lotes , Células CHO , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Proteínas Recombinantes/genética
7.
Nat Rev Immunol ; 20(10): 633-643, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32782358

RESUMO

Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Facilitadores/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Receptores de IgG/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Dengue/tratamento farmacológico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores de IgG/antagonistas & inibidores , Receptores de IgG/genética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais , Internalização do Vírus/efeitos dos fármacos
8.
PLoS One ; 15(5): e0233794, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470013

RESUMO

The domestic ferret (Mustela putorius furo) provides a critical animal model to study human respiratory diseases. However immunological insights are restricted due to a lack of ferret-specific reagents and limited genetic information about ferret B and T cell receptors. Here, variable, diversity and joining genes within the ferret kappa, lambda and heavy chain immunoglobulin loci were annotated using available genomic information. A multiplex PCR approach was derived that facilitated the recovery of paired heavy and light chain immunoglobulin sequences from single sorted ferret B cells, allowing validation of predicted germline gene sequences and the identification of putative novel germlines. Eukaryotic expression vectors were developed that enabled the generation of recombinant ferret monoclonal antibodies. This work advances the ferret as an informative immunological model for viral diseases by allowing the in-depth interrogation of antibody-based immunity.


Assuntos
Linfócitos B/imunologia , Modelos Animais de Doenças , Furões , Cadeias Leves de Imunoglobulina/genética , Receptores de Antígenos de Linfócitos B/genética , Animais , Anticorpos Monoclonais/biossíntese , Linfócitos B/citologia , Sequência de Bases , Furões/genética , Furões/imunologia , Genoma , Proteínas Recombinantes de Fusão/biossíntese
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(1): 69-74, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32314726

RESUMO

Objective To prepare the monoclonal antibodies (mAb) against hemagglutinin of H4 subtype avian influenza virus (AIV), and develop a sandwich ELISA for the detection of H4 subtype AIV. Methods The BALB/c mice were immunized with inactive H4 subtype AIV. A mAb against H4 subtype AIV, designated as 6G4, was obtained by cell fusion, hemagglutination inhibition (HI) screening and subcloing. Immuofluorescence cytochemistry and Western blotting were used to detect the reactivity of 6G4 with H4 subtype AIV, and the specificity, broad spectrum and stability of 6G4 were characterized by HI assay. Subclass of 6G4 was determined by kit. With chicken polyclonal antibody against H4 subtype AIV as coated antibody, 6G4 mAb as capture antibody and HRP-labeled goat anti-mouse IgG as the enzyme-labeled antibody, a sandwich ELISA for the detection of H4 subtype AIV was established by optimization of the reaction conditions and serial verification. Results 6G4 belonged to IgG1 subclass, and the light chain belonged to κ. It could secrete antibody stably and had good reactivity, specificity, broad spectrum and stability. ELISA based on 6G4 was specific, sensitive, accurate and suitable for the detection of a large number of samples. Conclusion We successfully achieved the anti-H4 subtype AIV mAb, and developed the sandwich ELISA for the detection of H4 subtype AIV.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Ensaio de Imunoadsorção Enzimática , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Testes de Inibição da Hemaglutinação , Vírus da Influenza A , Camundongos , Camundongos Endogâmicos BALB C
16.
Nat Commun ; 11(1): 1908, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313013

RESUMO

Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a "clean" Chinese hamster ovary (CHO) cell by disrupting multiple genes to eliminate HCPs. Using a model of CHO cell protein secretion, we predict that the elimination of unnecessary HCPs could have a non-negligible impact on protein production. We analyze the HCP content of 6-protein, 11-protein, and 14-protein knockout clones. These cell lines exhibit a substantial reduction in total HCP content (40%-70%). We also observe higher productivity and improved growth characteristics in specific clones. The reduced HCP content facilitates purification of a monoclonal antibody. Thus, substantial improvements can be made in protein titer and purity through large-scale HCP deletion, providing an avenue to increased quality and affordability of high-value biopharmaceuticals.


Assuntos
Engenharia Metabólica/métodos , Proteínas Recombinantes/biossíntese , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/isolamento & purificação , Produtos Biológicos , Células CHO , Cromatografia , Cricetulus , Técnicas de Inativação de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Rituximab , Biologia Sintética
17.
PLoS One ; 15(4): e0231770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298377

RESUMO

The Warburg effect, a hallmark of cancer, has recently been identified as a metabolic limitation of Chinese Hamster Ovary (CHO) cells, the primary platform for the production of monoclonal antibodies (mAb). Metabolic engineering approaches, including genetic modifications and feeding strategies, have been attempted to impose the metabolic prevalence of respiration over aerobic glycolysis. Their main objective lies in decreasing lactate production while improving energy efficiency. Although yielding promising increases in productivity, such strategies require long development phases and alter entangled metabolic pathways which singular roles remain unclear. We propose to apply drugs used for the metabolic therapy of cancer to target the Warburg effect at different levels, on CHO cells. The use of α-lipoic acid, a pyruvate dehydrogenase activator, replenished the Krebs cycle through increased anaplerosis but resulted in mitochondrial saturation. The electron shuttle function of a second drug, methylene blue, enhanced the mitochondrial capacity. It pulled on anaplerotic pathways while reducing stress signals and resulted in a 24% increase of the maximum mAb production. Finally, the combination of both drugs proved to be promising for stimulating Krebs cycle activity and mitochondrial respiration. Therefore, drugs used in metabolic therapy are valuable candidates to understand and improve the metabolic limitations of CHO-based bioproduction.


Assuntos
Anticorpos Monoclonais/biossíntese , Ciclo do Ácido Cítrico/fisiologia , Glicólise/efeitos dos fármacos , Engenharia Metabólica/métodos , Azul de Metileno/farmacologia , Ácido Tióctico/farmacologia , Animais , Células CHO , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Glucose/metabolismo , Glutamina/metabolismo , Glicólise/fisiologia , Ácido Láctico/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Azul de Metileno/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Respiração , Ácido Tióctico/metabolismo
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(2): 169-174, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32314715

RESUMO

Objective To prepare a monoclonal antibody (mAb) against human CD33 by immunizing mice with recombinant vector and analyze its characteristics and clinical application. Methods The eukaryotic expression vector pcDNA3.1(+)/CD33 was constructed and used to immunize mice. The mouse monoclonal antibody against human CD33 was then harvested using the hybridoma technique. Its properties were evaluated and the clinical performance was validated. Results One hybridoma cell line capable of secreting mouse anti-human CD33 monoclonal antibody was successfully obtained, which was named HI33a for clone identification with a subclass of IgG2a, κ. Flow Cytometry analysis revealed that the antibody could stain myeloid cell lines but not lymphoid cell lines, and it could inhibit the binding of similar imported antibodies with HL-60 cells competitively. Western blotting verified that it could bind a Mr 67 000 membrane protein extracted from HL-60 cells, which was a strong indication of the characteristics of CD33 protein molecule. Labeled with PE fluorescein, CD33-PE was tested as an antibody reagent in comparison with other similar imported products. Its overall performance including the accuracy, linearity, and precision all met the industrial standard. Further clinical evaluation of 558 bone marrow samples showed that the results were highly consistent with those by the imported reagents used as controls. Conclusion A hybridoma cell line stably secreting anti-human CD33 mAb was prepared.


Assuntos
Anticorpos Monoclonais/biossíntese , Hibridomas , Imunoglobulina G/biossíntese , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/antagonistas & inibidores , Animais , Especificidade de Anticorpos , Western Blotting , Humanos , Camundongos , Camundongos Endogâmicos BALB C
19.
PLoS One ; 15(4): e0229196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294099

RESUMO

Citrus mosaic virus (CiMV) is one of the causal viruses of citrus mosaic disease in satsuma mandarins (Citrus unshiu). Prompt detection of trees infected with citrus mosaic disease is important for preventing the spread of this disease. Although rabbit monoclonal antibodies (mAbs) exhibit high specificity and affinity, their applicability is limited by technical difficulties associated with the hybridoma-based technology used for raising these mAbs. Here, we demonstrate a feasible CiMV detection system using a specific rabbit mAb against CiMV coat protein. A conserved peptide fragment of the small subunit of CiMV coat protein was designed and used to immunize rabbits. Antigen-specific antibody-producing cells were identified by the immunospot array assay on a chip method. After cloning of variable regions in heavy or light chain by RT-PCR from these cells, a gene set of 33 mAbs was constructed and these mAbs were produced using Expi293F cells. Screening with the AlphaScreen system revealed eight mAbs exhibiting strong interaction with the antigen peptide. From subsequent sequence analysis, they were grouped into three mAbs denoted as No. 4, 9, and 20. Surface plasmon resonance analysis demonstrated that the affinity of these mAbs for the antigen peptide ranged from 8.7 × 10-10 to 5.5 × 10-11 M. In addition to CiMV, mAb No. 9 and 20 could detect CiMV-related viruses in leaf extracts by ELISA. Further, mAb No. 20 showed a high sensitivity to CiMV and CiMV-related viruses, simply by dot blot analysis. The anti-CiMV rabbit mAbs obtained in this study are envisioned to be extremely useful for practical applications of CiMV detection, such as in a virus detection kit.


Assuntos
Anticorpos Monoclonais/biossíntese , Citrus/virologia , Vírus do Mosaico/isolamento & purificação , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Especificidade de Anticorpos/imunologia , Proteínas do Capsídeo/imunologia , Cinética , Folhas de Planta/virologia , Coelhos
20.
Biotechnol Bioeng ; 117(7): 1990-2007, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32297972

RESUMO

High-quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA-dependent chaperone, in which the target antigen is genetically fused with an RNA-interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N-terminal tRNA-binding domain of lysyl-tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the "self" RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS-CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc-mediated effector function was demonstrated, which could be harnessed for the design of next-generation "universal" influenza vaccines. The nonimmunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Antivirais/biossíntese , Antígenos Virais/química , Infecções por Coronavirus/diagnóstico , Hibridomas/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Chaperonas Moleculares , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Antígenos Virais/genética , Antígenos Virais/imunologia , Infecções por Coronavirus/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Imunização , Vacinas contra Influenza , Lisina-tRNA Ligase/química , Lisina-tRNA Ligase/genética , Camundongos , Camundongos Endogâmicos BALB C , Conformação Proteica , Domínios Proteicos , Dobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Testes Sorológicos , Solubilidade
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