Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.458
Filtrar
1.
PLoS One ; 16(7): e0254367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242356

RESUMO

COVID-19 serological test must have high sensitivity as well as specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We have developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and common human coronavirus strains (229E, NL63, OC43, HKU1), and nucleocapsid (N) protein of SARS-CoV viruses. Receptor binding domain of S protein of SARS-CoV-2 (S-RBD), and N protein, demonstrated sensitivity (94% and 92.5%, respectively) in COVID-19 patients (n = 53), with 98% specificity in non-COVID-19 respiratory-disease (n = 98), and healthy-controls (n = 129). Anti S-RBD and N antibodies appeared five to ten days post-onset of symptoms, peaking at approximately four weeks. The appearance of IgG and IgM coincided while IgG subtypes, IgG1 and IgG3 appeared soon after the total IgG; IgG2 and IgG4 remained undetectable. Several inflammatory cytokines/chemokines were found to be elevated in many COVID-19 patients (e.g., Eotaxin, Gro-α, CXCL-10 (IP-10), RANTES (CCL5), IL-2Rα, MCP-1, and SCGF-b); CXCL-10 was elevated in all. In contrast to antibody titers, levels of CXCL-10 decreased with the improvement in patient health suggesting it as a candidate for disease resolution. Importantly, anti-N antibodies appear before S-RBD and differentiate between vaccinated and infected people-current vaccines (and several in the pipeline) are S protein-based.


Assuntos
Anticorpos Antivirais , COVID-19 , Quimiocinas , Proteínas do Nucleocapsídeo de Coronavírus , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Adulto , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Quimiocinas/sangue , Quimiocinas/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Coelhos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/imunologia
4.
Cell Rep ; 36(2): 109353, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34237283

RESUMO

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Sítios de Ligação , Linhagem Celular , Reações Cruzadas , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Camundongos , Testes de Neutralização , Ligação Proteica/imunologia , Domínios Proteicos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química
5.
Cell Rep ; 36(2): 109385, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34237284

RESUMO

Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-spike mAbs from two convalescent COVID-19 patients infected with prototypic SARS-CoV-2 by single-cell sorting of immunoglobulin-G-positive (IgG+) memory B cells. Anti-spike antibody induction is robust in these patients, and five mAbs have potent neutralizing activities. The efficacy of most neutralizing mAbs and convalescent plasma samples is maintained against B.1.1.7 and mink cluster 5 variants but is significantly decreased against variants B.1.351 from South Africa and P.1 from Brazil. However, mAbs with a high affinity for the receptor-binding domain remain effective against these neutralization-resistant variants. Rapid spread of these variants significantly impacts antibody-based therapies and vaccine strategies against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/imunologia , COVID-19/virologia , Linhagem Celular , Células HEK293 , Humanos , Imunização Passiva , Masculino , Mutação , Testes de Neutralização , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/genética
6.
Cell Rep ; 36(2): 109391, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34242574

RESUMO

The immunogenicity of the SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. In this study, we collect 2,360 COVID-19 sera and 601 control sera. We analyze these sera on a protein microarray with 20 proteins of SARS-CoV-2, building an antibody response landscape for immunoglobulin (Ig)G and IgM. Non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b, and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamics of non-structural/accessory proteins are different from those of the S and N proteins. The IgG responses against these six proteins are associated with disease severity and clinical outcome, and they decline sharply about 20 days after symptom onset. In non-survivors, a sharp decrease of IgG antibodies against S1 and N proteins before death is observed. The global antibody responses to non-structural/accessory proteins revealed here may facilitate a deeper understanding of SARS-CoV-2 immunology.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Proteínas não Estruturais Virais/imunologia , Proteínas Virais Reguladoras e Acessórias/imunologia , Adulto , Idoso , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Análise Serial de Proteínas
7.
Pediatr Infect Dis J ; 40(8): e294-e299, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34250968

RESUMO

INTRODUCTION: Antibody response developed within 2-3 weeks after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to decrease over time; however, there is limited data about antibody levels at 6 months or later postinfection, particularly in children. MATERIALS AND METHOD: A prospective multicenter study was performed using 315 samples of 74 confirmed and 10 probable coronavirus disease 2019 pediatric cases. About 20% of these cases were classified as asymptomatic, 74% as mild/moderate and 6% as severe/critical. Patients were included if at least 2 samples were available. The antibody response was classified as either early-period or late-period (14 days-3 months and after 6 months, respectively) for IgG response whereas IgA response was tested on various time intervals, including as early as 4 days up to 3 months. Euroimmun Anti-SARS-CoV-2 IgG and IgA and Genscript SARS-CoV-2 Surrogate Virus Neutralization Kits were used for antibody detection. RESULTS: There was no difference between the early-period and late-period IgG positivity (P = 0.1). However, the median IgG levels were 11.98 in the early periods and 4.05 in the late periods, with a significance of P < 0.001. Although the decrease in IgG levels was significant in asymptomatic and mild/moderate cases (P < 0.008 and P < 0.001, respectively), the decrease in severe/critical cases was moderate (P = 0.285). The sensitivity of the IgG after 15 days was higher than 94%, and the sensitivity of IgA was 88% on days 8-15. CONCLUSION: SARS-CoV-2 IgG antibody levels decreased after 6 months. The decrease was moderate in severe/critical cases. Overall, 95.8% of the patients remained positive up to 9 months after infection. Although the IgA response may be useful early on, the IgG response is useful after 14 days.


Assuntos
Anticorpos Antivirais/biossíntese , COVID-19/imunologia , SARS-CoV-2/imunologia , Adolescente , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunoglobulina A , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Lactente , Estudos Longitudinais , Masculino , Estudos Prospectivos
8.
Front Immunol ; 12: 684014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194438

RESUMO

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.


Assuntos
Anafilatoxinas/metabolismo , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/fisiopatologia , Progressão da Doença , ELISPOT , Feminino , Citometria de Fluxo , Humanos , Imunidade Humoral , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente
9.
Viruses ; 13(6)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207378

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is genetically variable, allowing it to adapt to various hosts including humans. Indeed, SARS-CoV-2 has accumulated around two mutations per genome each month. The first relevant event in this context was the occurrence of the mutant D614G in the Spike gene. Moreover, several variants have emerged, including the well-characterized 20I/501Y.V1, 20H/501Y.V2, and 20J/501Y.V3 strains, in addition to those that have been detected within clusters, such as 19B/501Y or 20C/655Y in France. Mutants have also emerged in animals, including a variant transmitted to humans, namely, the Mink variant detected in Denmark. The emergence of these variants has affected the transmissibility of the virus (for example, 20I/501Y.V1, which was up to 82% more transmissible than other preexisting variants), its severity, and its ability to escape natural, adaptive, vaccine, and therapeutic immunity. In this respect, we review the literature on variants that have currently emerged, and their effect on vaccines and therapies, and, in particular, monoclonal antibodies (mAbs). The emergence of SARS-CoV-2 variants must be examined to allow effective preventive and curative control strategies to be developed.


Assuntos
Anticorpos Monoclonais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/terapia , Mutação , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/transmissão , Vacinas contra COVID-19/administração & dosagem , Humanos , SARS-CoV-2/genética
10.
Front Immunol ; 12: 678570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211469

RESUMO

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Técnicas de Visualização da Superfície Celular/métodos , Mineração de Dados/métodos , Epitopos/imunologia , Humanos , Imunização Passiva/métodos
11.
Front Immunol ; 12: 687869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220844

RESUMO

To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs. However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Linhagem Celular , Células HEK293 , Humanos , Imunização Passiva , Camundongos , Testes de Neutralização/métodos , Reino Unido , Vacinação
12.
PLoS One ; 16(7): e0253977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214116

RESUMO

SARS-CoV-2 pandemic is causing high morbidity and mortality burden worldwide with unprecedented strain on health care systems. To investigate the time course of the antibody response in relation to the outcome we performed a study in hospitalized COVID-19 patients. As comparison we also investigated the time course of the antibody response in SARS-CoV-2 asymptomatic subjects. Study results show that patients produce a strong antibody response to SARS-CoV-2 with high correlation between different viral antigens (spike protein and nucleoprotein) and among antibody classes (IgA, IgG, and IgM and neutralizing antibodies). The antibody peak is reached by 3 weeks from hospital admission followed by a sharp decrease. No difference was observed in any parameter of the antibody classes, including neutralizing antibodies, between subjects who recovered or with fatal outcome. Only few asymptomatic subjects developed antibodies at detectable levels.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas , COVID-19/imunologia , SARS-CoV-2/imunologia , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/mortalidade , Comorbidade , Feminino , Hospitalização , Humanos , Imunoglobulina A/biossíntese , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/biossíntese , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos
13.
Med Sci Monit ; 27: e930168, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34193809

RESUMO

Coronavirus Disease-2019 (COVID-19) is a rapidly spreading pandemic that began at the end of 2019. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reproductive health has always been one of the most important healthcare problems, and the impacts of COVID-19 on the reproductive systems have become an emerging topic. The effects of infection with SARS-CoV-2 on males are more harmful than on females. The outcomes of pregnancy also can show the condition of male and female reproductive system health. The vertical transmission of SARS-CoV-2 significantly affects pregnancy healthy. SARS-CoV-2, antibody, and other factors, such as the decline of lymphocyte counts, and increased erythrocyte sedimentation rate, C-reactive protein, and D-dimer levels, are evidence of SARS-CoV-2 vertical transmission. Angiotensin-converting enzyme 2 (ACE2) is regarded as a virus receptor in the reproductive system. The expression and activity of ACE2 are influenced by sex hormones, especially the male sex hormones. The strength of immunity is crucial to fighting off viral infection. Antibodies against SARS-CoV-2 show different expression in male and female patients, and the antibodies have been regarded as having potential applications in COVID-19 prevention and treatment. This review aims to present the current status of what is known about the involvement of the male and female reproductive systems, as well as the effects on pregnancy health, during infection with SARS-CoV-2, and discusses the implications for future fertility.


Assuntos
COVID-19/epidemiologia , Genitália/imunologia , Complicações Infecciosas na Gravidez/epidemiologia , Saúde Reprodutiva , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/complicações , COVID-19/imunologia , COVID-19/transmissão , Feminino , Fertilidade/imunologia , Hormônios Esteroides Gonadais/metabolismo , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Fatores de Risco , SARS-CoV-2/patogenicidade , Fatores Sexuais , Internalização do Vírus
14.
Signal Transduct Target Ther ; 6(1): 256, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234102

RESUMO

We collected blood from coronavirus disease 2019 (COVID-19) convalescent individuals and investigated SARS-CoV-2-specific humoral and cellular immunity in these discharged patients. Follow-up analysis in a cohort of 171 patients at 4-11 months after the onset revealed high levels of IgG antibodies. A total of 78.1% (164/210) of the specimens tested positive for neutralizing antibody (NAb). SARS-CoV-2 antigen peptide pools-stimulated-IL-2 and -IFN-γ response can distinguish COVID-19 convalescent individuals from healthy donors. Interestingly, NAb survival was significantly affected by the antigen peptide pools-stimulated-IL-2 response, -IL-8 response, and -IFN-γ response. The antigen peptide pools-activated CD8+ T cell counts were correlated with NAb. The antigen peptide pools-activated natural killer (NK) cell counts in convalescent individuals were correlated with NAb and disease severity. Our data suggested that the development of NAb is associated with the activation of T cells and NK cells. Our work provides a basis for further analysis of the protective immunity to SARS-CoV-2 and for understanding the pathogenesis of COVID-19. It also has implications for the development of an effective vaccine for SARS-CoV-2 infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Convalescença , Citocinas/imunologia , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/imunologia , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Front Immunol ; 12: 659071, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234774

RESUMO

SARS-CoV-2 is a newly emerged betacoronavirus and the causative agent for the COVID-19 pandemic. Antibodies recognizing the viral spike protein are instrumental in natural and vaccine-induced immune responses to the pathogen and in clinical diagnostic and therapeutic applications. Unlike conventional immunoglobulins, the variable lymphocyte receptor antibodies of jawless vertebrates are structurally distinct, indicating that they may recognize different epitopes. Here we report the isolation of monoclonal variable lymphocyte receptor antibodies from immunized sea lamprey larvae that recognize the spike protein of SARS-CoV-2 but not of other coronaviruses. We further demonstrate that these monoclonal variable lymphocyte receptor antibodies can efficiently neutralize the virus and form the basis of a rapid, single step SARS-CoV-2 detection system. This study provides evidence for monoclonal variable lymphocyte receptor antibodies as unique biomedical research and potential clinical diagnostic reagents targeting SARS-CoV-2.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Proteínas de Peixes/imunologia , Petromyzon/imunologia , SARS-CoV-2/fisiologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Neutralizantes/genética , Anticorpos Antivirais/genética , Evolução Biológica , Reações Cruzadas , Epitopos de Linfócito B/imunologia , Proteínas de Peixes/genética , Humanos
16.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34193524

RESUMO

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.


Assuntos
Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Chlorocebus aethiops , Feminino , Humanos , Masculino , Mesocricetus , Pandemias , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Vacinas Atenuadas/imunologia , Células Vero
18.
Nat Commun ; 12(1): 4196, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234131

RESUMO

Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.


Assuntos
Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , COVID-19/imunologia , Epitopos , Antígenos HLA/imunologia , Humanos , Evasão da Resposta Imune/genética , Modelos Moleculares , Mutação , Testes de Neutralização , Domínios Proteicos , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química
19.
Nat Commun ; 12(1): 4210, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244522

RESUMO

Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Receptores Virais/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Sítios de Ligação/imunologia , COVID-19/imunologia , Cricetinae , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Humanos , Masculino , Testes de Neutralização , Receptores de Antígenos de Linfócitos B/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
20.
Rev Med Virol ; 31(4): e2195, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260780

RESUMO

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , COVID-19/patologia , Citocinas/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Leucócitos/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...