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2.
Clin Infect Dis ; 72(2): 301-308, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33543254

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. METHODS: Sera (n = 533) from patients with real-time polymerase chain reaction-confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. RESULTS: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. CONCLUSIONS: High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.


Assuntos
Formação de Anticorpos , Anticorpos Antivirais , Humanos , Imunoglobulina M , Cinética , Estudos Soroepidemiológicos , Índice de Gravidade de Doença
3.
PLoS One ; 16(2): e0246731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33571241

RESUMO

SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.


Assuntos
Anticorpos Neutralizantes/imunologia , Epitopos de Linfócito B/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Motivos de Aminoácidos , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Linfócitos B/imunologia , Simulação por Computador , Epitopos de Linfócito B/química , Humanos , Modelos Moleculares , Peptídeos/química , Peptídeos/imunologia , Glicoproteína da Espícula de Coronavírus/química , Linfócitos T/imunologia
4.
Arch Virol ; 166(2): 571-579, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410993

RESUMO

This study compared concurrent and separate primary vaccination against equid alphaherpesviruses 1 and 4, genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and equine influenza A virus, genus Alphainfluenzavirus, family Orthomyxoviridae. Their vernacular names are equine herpesvirus 1 and 4 (EHV1/4) and equine influenza virus (EIV). Infection with these respiratory pathogens is associated with loss of performance, interruption of training schedules, and on occasion, cancellation of equestrian events. Vaccination is highly recommended, and for some activities it is a mandatory requirement of the relevant authority. As there is a dearth of information relating to the impact of concurrent vaccination on the antibody response to EHV and EIV vaccines, they are usually administered separately, often 2 weeks apart. In a previous study of booster vaccination in Thoroughbred racehorses, concurrent vaccination with whole-virus inactivated carbopol-adjuvanted EHV and EIV vaccines did not impact negatively on the antibody response. In this study, investigations were extended to concurrent versus separate primary vaccination of warmblood foals. A field study was conducted to compare the immune response to a carbopol-adjuvanted EHV vaccine and an immune stimulating complex (ISCOM)-adjuvanted EI vaccine administered concurrently and 2 weeks apart. No adverse clinical reactions were observed, the pattern of EI and EHV antibody response was similar for both groups, and there was no evidence that concurrent primary vaccination compromised the humoral response. The results are of relevance to horse owners who wish to decrease veterinary costs, limit handling of young animals, and simplify record keeping by vaccinating concurrently.


Assuntos
Infecções por Herpesviridae/imunologia , Vacinas contra Herpesvirus/imunologia , Doenças dos Cavalos/imunologia , Cavalos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Feminino , Doenças dos Cavalos/virologia , Cavalos/virologia , Imunidade Humoral/imunologia , Imunização Secundária/métodos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia
5.
Sheng Wu Gong Cheng Xue Bao ; 37(1): 290-300, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33501809

RESUMO

For improving epitope immunogenicity and achieving the co-immunization, late protein 1 (L1) of HPV type 16 (HPV16L1) was selected as the vector to carry the dominant epitope of Toxoplasma gondii because of the shared common population between Toxoplasma gondii and human papillomavirus (HPV). RSepitope-HPV16L1 (RSepitope fused at the "N-terminus" of HPV16L1) and HPV16L1-RSepitope (RSepitope fused at the "C-terminus" of HPV16L1) chimeras were constructed. After transfection of COS-7 cells with the recombinants, Western blot, RT-PCR, and immunofluorescence experiments confirmed that RSepitope-HPV16L1 could successfully express the corresponding mRNA and protein of RSepitope and HPV16L1, but the HPV16L1-RSepitope construct could not. A "prime-boost" immunization program was applied in mice to further evaluate the immune response elicited by the constructs, and the RSepitope-HPV16L1 immunization group produced the most significantly increased humoral and cellular immune responses (the highest RSepitope-specific IgG antibody level and the highest IFN-γ production, respectively), in which both elevated Th1 and Th2 immune responses were obtained. Moreover, the advantage of HPV16L1 as an epitope carrier was remarkable for RSepitope-HPV16L1, which induced a more prominent immunological response than RSepitope alone (without fusion with HPV16L1). Our research indicated that the N-terminus of HPV16L1 could be a better insertion site for enhancing target epitope immunogenicity, and our study offers a design for epitope vaccine of reasonable combination.


Assuntos
Toxoplasma , Vacinas de DNA , Animais , Formação de Anticorpos , Epitopos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Vacinação
6.
PLoS Pathog ; 17(1): e1009161, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444413

RESUMO

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.


Assuntos
/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Argentina/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Soroepidemiológicos
7.
Clin Infect Dis ; 72(2): 301-308, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501951

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. METHODS: Sera (n = 533) from patients with real-time polymerase chain reaction-confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. RESULTS: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. CONCLUSIONS: High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.


Assuntos
Formação de Anticorpos , Anticorpos Antivirais , Humanos , Imunoglobulina M , Cinética , Estudos Soroepidemiológicos , Índice de Gravidade de Doença
8.
BMJ Case Rep ; 14(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514621

RESUMO

Around the world, with the availability of factor concentrates, patients with haemophilia have undergone major and minor surgeries. Inhibitor development in early postoperative period leading to inadequate factor recovery and ongoing bleeding is a nightmare for both operating surgeon as well as haematologists. We describe a case of an elderly man with mild haemophilia A, who was diagnosed with pancreatic carcinoma and underwent Whipple's procedure. After an uneventful procedure, he developed high-titre inhibitors and bleeding a week after surgery posing major challenges in his management. The case highlights the importance of experienced surgeons, trained haematologists, regular monitoring of factor assay/inhibitors, adequate factor and bypassing-agent support while performing such procedures.


Assuntos
Fatores de Coagulação Sanguínea/antagonistas & inibidores , Hemofilia A/imunologia , Neoplasias Pancreáticas/cirurgia , Hemorragia Pós-Operatória/tratamento farmacológico , Idoso , Formação de Anticorpos/imunologia , Fatores de Coagulação Sanguínea/imunologia , Fator VIII/administração & dosagem , Fator VIII/uso terapêutico , Evolução Fatal , Hematologia/normas , Hemofilia A/complicações , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Hemorragias Intracranianas/complicações , Masculino , Neoplasias Pancreáticas/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Hemorragia Pós-Operatória/etiologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Fatores de Risco , Cirurgiões/estatística & dados numéricos
9.
Artigo em Inglês | MEDLINE | ID: mdl-33361386

RESUMO

OBJECTIVE: To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML). METHODS: Review of pertinent literature. RESULTS: There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4+ T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell-mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response. CONCLUSION: Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2-specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.


Assuntos
Imunidade Adaptativa/imunologia , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Imunidade Humoral/imunologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Linfócitos T/imunologia , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico
10.
Nat Med ; 27(2): 279-288, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33335322

RESUMO

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.


Assuntos
Formação de Anticorpos/imunologia , /imunologia , Imunização Secundária , /imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Relação Dose-Resposta a Droga , Vetores Genéticos/imunologia , Humanos , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo , Adulto Jovem
11.
Nat Med ; 27(2): 270-278, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33335323

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.


Assuntos
Formação de Anticorpos/imunologia , Linfócitos T/imunologia , Adolescente , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , /virologia , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Subunidades Proteicas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto Jovem
12.
PLoS One ; 15(12): e0244126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382764

RESUMO

BACKGROUND: Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. METHODS: Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. RESULTS: 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14-22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. CONCLUSIONS: Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , /imunologia , Reações Cruzadas , Feminino , Humanos , Masculino , /metabolismo
14.
Virol Sin ; 35(6): 820-829, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33351168

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human health and the economy. Currently, long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited. Herein, we report the clinical features, viral RNA loads, and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People's Hospital, Hubei Province, China. Overall, 5.36% (6/112) of patients showed persistent viral RNA shedding (> 45 days). The peak viral load was higher in the severe disease group than in the mild group (median cycle threshold value, 36.4 versus 31.5; P = 0.002). For most patients the disappearance of IgM antibodies occurred approximately 4-6 weeks after symptoms onset, while IgG persisted for over 194 days after the onset of symptoms, although patients showed a 46% reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase. We also studied 18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients, and the asymptomatic individuals were the close contacts of these symptomatic cases. Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals. These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection, and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/imunologia , /imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Formação de Anticorpos , /virologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Cinética , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Carga Viral , Eliminação de Partículas Virais
17.
Diabetologia ; 63(12): 2548-2558, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33029657

RESUMO

AIMS/HYPOTHESIS: The aim of the study was to characterise the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with diabetes. Demonstrating the ability to mount an appropriate antibody response in the presence of hyperglycaemia is relevant for the comprehension of mechanisms related to the observed worse clinical outcome of coronavirus disease 2019 (COVID-19) pneumonia in patients with diabetes and for the development of any future vaccination campaign to prevent SARS-CoV-2 infection. METHODS: Using a highly specific and sensitive measurement of antibodies by fluid-phase luciferase immunoprecipitation assays, we characterised the IgG, IgM and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with documented diagnosis of COVID-19, prospectively followed at our institution. We analysed clinical outcomes and antibody titres according to the presence of hyperglycaemia, i.e., either diagnosed or undiagnosed diabetes, at the time of, or during, hospitalisation. RESULTS: Among patients with confirmed COVID-19, 139 (27.3%) had diabetes: 90 (17.7%) had diabetes diagnosed prior to the hospital admission (comorbid diabetes) while 49 (9.6%) had diabetes diagnosed at the time of admission (newly diagnosed). Diabetes was associated with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leucocytosis and neutrophilia. Diabetes was independently associated with risk of death (HR 2.32 [95% CI 1.44, 3.75], p = 0.001), even after adjustment for age, sex and other relevant comorbidities. Moreover, a strong association between higher glucose levels and risk of death was documented irrespective of diabetes diagnosis (HR 1.14 × 1.1 mmol/l [95% CI 1.08, 1.21], p < 0.001). The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable, as for timing and antibody titres, to that of non-diabetic patients, with marginal differences, and was not influenced by glucose levels. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike receptor-binding domain (RBD) was predictive of survival rate, both in the presence or absence of diabetes. CONCLUSIONS/INTERPRETATION: The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycaemia was not the result of an impaired humoral response against SARS-CoV-2. RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARs-COV-2 in people with diabetes. Graphical abstract.


Assuntos
Formação de Anticorpos , Antígenos Virais/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Biomarcadores/análise , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/imunologia , Glicemia/análise , Estudos de Coortes , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Imunidade Humoral , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Fatores de Risco , Análise de Sobrevida
18.
Cell Host Microbe ; 28(4): 499-501, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33031765

RESUMO

In this issue of Cell Host & Microbe, Nielsen and colleagues sequence antibody repertoires of patients with severe COVID-19 to reveal potentially convergent features on the background of a larger, polyclonal response. Their findings suggest that, as databases improve, it may be possible to monitor virus-specific B cells after infection or vaccination using antibody sequencing.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave , Anticorpos Antivirais , Formação de Anticorpos , Linfócitos B , Betacoronavirus , Humanos , Imunoglobulina G
19.
J Vet Sci ; 21(5): e74, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016020

RESUMO

BACKGROUND: The quality of a vaccine depends strongly on the effects of the adjuvants applied simultaneously with the antigen in the vaccine. The adjuvants enhance the protective effect of the vaccine against a viral challenge. Conversely, oil-type adjuvants leave oil residue inside the bodies of the injected animals that can produce a local reaction in the muscle. The long-term immunogenicity of mice after vaccination was examined. ISA206 or ISA15 oil adjuvants maintained the best immunity, protective capability, and safety among the oil adjuvants in the experimental group. OBJECTIVES: This study screened the adjuvant composites aimed at enhancing foot-and-mouth disease (FMD) immunity. The C-type lectin or toll-like receptor (TLR) agonist showed the most improved protection rate. METHODS: Experimental vaccines were fabricated by mixing various known oil adjuvants and composites that can act as immunogenic adjuvants (gel, saponin, and other components) and examined the enhancement effect on the vaccine. RESULTS: The water in oil (W/O) and water in oil in water (W/O/W) adjuvants showed better immune effects than the oil in water (O/W) adjuvants, which have a small volume of oil component. The W/O type left the largest amount of oil residue, followed by W/O/W and O/W types. In the mouse model, intramuscular inoculation showed a better protection rate than subcutaneous inoculation. Moreover, the protective effect was particularly weak in the case of inoculation in fatty tissue. The initial immune reaction and persistence of long-term immunity were also confirmed in an immune reaction on pigs. CONCLUSIONS: The new experimental vaccine with immunostimulants produces improved immune responses and safety in pigs than general oil-adjuvanted vaccines.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Doenças dos Suínos/prevenção & controle , Vacinação/veterinária , Vacinas Virais/farmacologia , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Febre Aftosa/imunologia , Febre Aftosa/virologia , Camundongos , Camundongos Endogâmicos C57BL , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Vacinas Virais/imunologia
20.
PLoS One ; 15(10): e0240502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035234

RESUMO

BACKGROUND: A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. METHODS: Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. RESULTS: A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8-93.6) and 84.8% (95% CI: 76.2-91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). CONCLUSION: The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Formação de Anticorpos , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Estudos de Casos e Controles , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Fatores Sexuais , Glicoproteína da Espícula de Coronavírus/imunologia
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