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2.
Int Immunol ; 33(10): 529-540, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1467360

RESUMO

Coronavirus disease 2019 (COVID-19) has caused millions of deaths, and serious consequences to public health, economies and societies. Rapid responses in vaccine development have taken place since the isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the release of the viral genome sequence. By 21 May 2021, 101 vaccines were under clinical trials, and published data were available for 18 of them. Clinical study results from some vaccines indicated good immunogenicity and acceptable reactogenicity. Here, we focus on these 18 vaccines that had published clinical data to dissect the induced humoral and cellular immune responses as well as their safety profiles and protection efficacy.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Animais , Humanos , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia
3.
Ann Intern Med ; 174(6): 811-821, 2021 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1456489

RESUMO

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear. LIMITATIONS: Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy. CONCLUSION: Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).


Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos , COVID-19/imunologia , Pneumonia Viral/imunologia , SARS-CoV-2/imunologia , Especificidade de Anticorpos/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
6.
J Hepatol ; 75(2): 439-441, 2021 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1454288

RESUMO

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19 , Imunogenicidade da Vacina/imunologia , Hepatopatia Gordurosa não Alcoólica , Vacinação , Vacinas de Produtos Inativados , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , China/epidemiologia , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Vacinação/métodos , Vacinação/estatística & dados numéricos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos
7.
J Hepatol ; 75(2): 435-438, 2021 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1454287

RESUMO

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina/imunologia , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Transplante de Fígado/métodos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Imunossupressão/métodos , Israel/epidemiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/imunologia , Testes Sorológicos/métodos , Testes Sorológicos/estatística & dados numéricos , Vacinação/efeitos adversos , Vacinação/métodos
8.
J Med Virol ; 93(10): 5816-5824, 2021 10.
Artigo em Inglês | MEDLINE | ID: covidwho-1453607

RESUMO

Serological testing for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme-linked immunosorbent assays. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information on whether or not the individual has been infected with SARS-CoV-2. Enzyme-linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Isotipos de Imunoglobulinas/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Environ Health Prev Med ; 26(1): 99, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1448180

RESUMO

OBJECTIVES: In this article, we aim to share our experience in the hospital reorganization made to conduct the SARS-CoV-2 vaccination campaign, based on the principles of flexibility and adaptability. STUDY DESIGN: A descriptive study. METHODS: The data concerning the organization of the vaccination campaign were taken from the operative protocol developed by the hospital dedicated task force, composed by experts in hygiene, public health, occupational medicine, pharmacists, nurses, hospital quality, and disaster managers. Data about the numbers of vaccine administered daily were collected by the Innovation and Development Operative Unit database. RESULTS: Vaccinations against COVID-19 started across the EU on the 27th of December 2020. The first phase of the vaccination campaign carried out in our hospital was directed to healthcare workers immunization including medical residents, social care operators, administrative staff and technicians, students of medicine, and health professions trainees. The second phase was enlarged to the coverage of extremely fragile subjects. Thanks to the massive employment of healthcare workers and the establishment of dynamic pathways, it was possible to achieve short turnaround times and a large number of doses administered daily, with peaks of 870 vaccines per day. From the 27th of December up to the 14th of March a total of 26,341 doses of Pfizer have been administered. 13,584 were first doses and 12,757 were second doses. From the 4th to the 14th of March, 296 first doses of Moderna were dispensed. It was necessary to implement adequate spaces and areas adopting anti-contagion safety measures: waiting area for subjects to be vaccinated, working rooms for the dilution of the vaccine and the storage of the material, vaccination rooms, post-vaccination observation areas, room for observation, and treatment of any adverse reactions, with an emergency cart available in each working area. CONCLUSIONS: The teaching hospital of Pisa faced the beginning of the immunization campaign readjusting its spaces, planning an adequate hospital vaccination area and providing an organization plan to ensure the achievement of the targets of the campaign. This represented a challenge due to limited vaccine doses supplied and the multisectoral teams of professionals to coordinate in the shortest time and the safest way possible. The organizational model adopted proved to be adequate and therefore exploited also for the second phase aimed to extremely fragile subjects.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Programas de Imunização/organização & administração , SARS-CoV-2/imunologia , Hospitais de Ensino/organização & administração , Humanos , Itália/epidemiologia
12.
Immunol Invest ; 50(7): 743-779, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: covidwho-1447461

RESUMO

COVID-19, the disease caused by the novel severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), was first detected in December 2019 and has since morphed into a global pandemic claiming over 2.4 million human lives and severely impacting global economy. The race for a safe and efficacious vaccine was thus initiated with government agencies as well as major pharmaceutical companies as frontrunners. An ideal vaccine would activate multiple arms of the adaptive immune system to generate cytotoxic T cell responses as well as neutralizing antibody responses, while avoiding pathological or deleterious immune responses that result in tissue damage or exacerbation of the disease. Developing an effective vaccine requires an inter-disciplinary effort involving virology, protein biology, biotechnology, immunology and pharmaceutical sciences. In this review, we provide a brief overview of the pathology and immune responses to SARS-CoV-2, which are fundamental to vaccine development. We then summarize the rationale for developing COVID-19 vaccines and provide novel insights into vaccine development from a pharmaceutical science perspective, such as selection of different antigens, adjuvants, delivery platforms and formulations. Finally, we review multiple clinical trial outcomes of novel vaccines in terms of safety and efficacy.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Ensaios Clínicos como Assunto , Humanos , Pandemias/prevenção & controle , SARS-CoV-2/imunologia
13.
Proc Natl Acad Sci U S A ; 118(42)2021 10 01.
Artigo em Inglês | MEDLINE | ID: covidwho-1447423

RESUMO

Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Monoclonais/biossíntese , Glicosilação , Humanos , Testes de Neutralização , Proteínas Recombinantes/biossíntese
14.
Front Immunol ; 12: 740249, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1448730

RESUMO

Objective: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. Methods: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. Results: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. Conclusion: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.


Assuntos
Anticorpos Antivirais/imunologia , Artrite Reumatoide/terapia , Vacinas contra COVID-19/imunologia , Imunoterapia/efeitos adversos , Linfócitos T/imunologia , Idoso , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , COVID-19/prevenção & controle , Feminino , Humanos , Interferon gama/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/citologia , Vacinas Sintéticas/imunologia
15.
Front Immunol ; 12: 739037, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1448729

RESUMO

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.


Assuntos
COVID-19/terapia , Convalescença , SARS-CoV-2/imunologia , Soroconversão , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Doadores de Sangue , COVID-19/sangue , COVID-19/imunologia , Feminino , Humanos , Imunização Passiva , Cinética , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , RNA Viral/sangue
16.
Biochem Biophys Res Commun ; 574: 14-19, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: covidwho-1446453

RESUMO

Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant's receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding ß-loop-ß motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , COVID-19/imunologia , Evasão da Resposta Imune/imunologia , Mutação/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Aminoácidos/genética , Aminoácidos/imunologia , Aminoácidos/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Antivirais/imunologia , Sítios de Ligação/genética , Sítios de Ligação/imunologia , COVID-19/metabolismo , COVID-19/virologia , Humanos , Evasão da Resposta Imune/genética , Simulação de Dinâmica Molecular , Mutação/genética , Testes de Neutralização , Ligação Proteica , Domínios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética
17.
Gigascience ; 10(9)2021 09 28.
Artigo em Inglês | MEDLINE | ID: covidwho-1443047

RESUMO

BACKGROUND: B-cell immunoglobulin repertoires with paired heavy and light chain can be determined by means of 10X single-cell V(D)J sequencing. Precise and quick analysis of 10X single-cell immunoglobulin repertoires remains a challenge owing to the high diversity of immunoglobulin repertoires and a lack of specialized software that can analyze such diverse data. FINDINGS: In this study, specialized software for 10X single-cell immunoglobulin repertoire analysis was developed. SCIGA (Single-Cell Immunoglobulin Repertoire Analysis) is an easy-to-use pipeline that performs read trimming, immunoglobulin sequence assembly and annotation, heavy and light chain pairing, statistical analysis, visualization, and multiple sample integration analysis, which is all achieved by using a 1-line command. Then SCIGA was used to profile the single-cell immunoglobulin repertoires of 9 patients with coronavirus disease 2019 (COVID-19). Four neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified from these repertoires. CONCLUSIONS: SCIGA provides a complete and quick analysis for 10X single-cell V(D)J sequencing datasets. It can help researchers to interpret B-cell immunoglobulin repertoires with paired heavy and light chain.


Assuntos
Imunoglobulinas/metabolismo , Análise de Célula Única/métodos , Software , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , COVID-19/patologia , COVID-19/virologia , Humanos , Imunoglobulinas/química , Imunoglobulinas/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação
18.
MAbs ; 13(1): 1978130, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1442969

RESUMO

Recent years have seen unparalleled development of microfluidic applications for antibody discovery in both academic and pharmaceutical research. Microfluidics can support native chain-paired library generation as well as direct screening of antibody secreting cells obtained by rodent immunization or from the human peripheral blood. While broad diversities of neutralizing antibodies against infectious diseases such as HIV, Ebola, or COVID-19 have been identified from convalescent individuals, microfluidics can expedite therapeutic antibody discovery for cancer or immunological disease indications. In this study, a commercially available microfluidic device, Cyto-Mine, was used for the rapid identification of natively paired antibodies from rodents or human donors screened for specific binding to recombinant antigens, for direct screening with cells expressing the target of interest, and, to our knowledge for the first time, for direct broad functional IgG antibody screening in droplets. The process time from cell preparation to confirmed recombinant antibodies was four weeks. Application of this or similar microfluidic devices and methodologies can accelerate and enhance pharmaceutical antibody hit discovery.


Assuntos
Anticorpos Neutralizantes/isolamento & purificação , Imunoglobulina G/isolamento & purificação , Microfluídica/métodos , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/isolamento & purificação , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/isolamento & purificação , Especificidade de Anticorpos , Antígenos/imunologia , Antígenos de Neoplasias/imunologia , Preservação de Sangue , COVID-19/imunologia , Transferência Ressonante de Energia de Fluorescência , Humanos , Hibridomas/imunologia , Separação Imunomagnética , Dispositivos Lab-On-A-Chip , Camundongos , Microfluídica/instrumentação , Muromonab-CD3/imunologia , Plasmócitos , Proteínas Recombinantes/imunologia , SARS-CoV-2/imunologia , Toxoide Tetânico/imunologia , Vacinação
19.
Nature ; 597(7878): 703-708, 2021 09.
Artigo em Inglês | MEDLINE | ID: covidwho-1442788

RESUMO

SARS-CoV-2 infections have surged across the globe in recent months, concomitant with considerable viral evolution1-3. Extensive mutations in the spike protein may threaten the efficacy of vaccines and therapeutic monoclonal antibodies4. Two signature spike mutations of concern are E484K, which has a crucial role in the loss of neutralizing activity of antibodies, and N501Y, a driver of rapid worldwide transmission of the B.1.1.7 lineage. Here we report the emergence of the variant lineage B.1.526 (also known as the Iota variant5), which contains E484K, and its rise to dominance in New York City in early 2021. This variant is partially or completely resistant to two therapeutic monoclonal antibodies that are in clinical use and is less susceptible to neutralization by plasma from individuals who had recovered from SARS-CoV-2 infection or serum from vaccinated individuals, posing a modest antigenic challenge. The presence of the B.1.526 lineage has now been reported in all 50 states in the United States and in many other countries. B.1.526 rapidly replaced earlier lineages in New York, with an estimated transmission advantage of 35%. These transmission dynamics, together with the relative antibody resistance of its E484K sub-lineage, are likely to have contributed to the sharp rise and rapid spread of B.1.526. Although SARS-CoV-2 B.1.526 initially outpaced B.1.1.7 in the region, its growth subsequently slowed concurrently with the rise of B.1.1.7 and ensuing variants.


Assuntos
COVID-19/virologia , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/isolamento & purificação , Anticorpos Neutralizantes/imunologia , Humanos , Mutação , New York/epidemiologia , Filogenia , Filogeografia , Prevalência , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Estados Unidos/epidemiologia
20.
Signal Transduct Target Ther ; 6(1): 315, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1442755

RESUMO

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Anticorpos Monoclonais Murinos/farmacologia , Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Anticorpos Monoclonais Murinos/imunologia , Antivirais/imunologia , Chlorocebus aethiops , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Células Vero
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