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1.
Indian J Med Res ; 153(1 & 2): 64-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33818467

RESUMO

Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.


Assuntos
/terapia , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunização Passiva , Índia/epidemiologia
2.
Front Immunol ; 12: 653189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828563

RESUMO

After the pandemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 have been developed for the prophylactic and therapeutic purposes. However, few methodologies are described in detail on how to rapidly and efficiently generate effective NAbs to SARS-CoV-2. Here, we integrated and optimized a strategically screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific NAbs within 6 days, followed by additional 9 days for antibody production and function analysis. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited advanced neutralizing potency and high affinity, with the top two NAbs showing half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides an effective methodology with high applicable value for discovering potential preventative and therapeutic NAbs for the emerging infectious diseases.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , /imunologia , Humanos , /metabolismo
3.
PLoS One ; 16(4): e0248813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831032

RESUMO

Healthcare personnel are at risk to aquire the corona virus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the prevalence of SARS-CoV-2 antibodies and positive nasopharyngeal reverse transcriptase polymerase-chain reaction (RT-PCR) tests in German intensive care and emergency physicians. Physicians attending intensive care and emergency medicine training courses between June 16th and July 2nd 2020 answered a questionnaire and were screened for SARS-CoV-2 antibodies via automated electrochemiluminiscence immunoassay. We recruited 516 physicans from all parts of Germany, 445/516 (86%) worked in high risk areas, and 379/516 (73%) had treated patients with COVID-19. The overall positive rate was 18/516 (3.5%), 16/18 (89%) had antibodies against SARS-COV-2, another 2 reported previous positive RT-PCR results although antibody testing was negative. Of those positive, 7/18 (39%) were unaware of their infection. A stay abroad was stated by 173/498 (35%), mostly in Europe. 87/516 (17%) reported a febrile respiratory infection after January 1st 2020 which was related to SARS-CoV-2 in 4/87 (4.6%). Contact to COVID-19 positive relatives at home was stated by 22/502 (4.4%). This was the only significant risk factor for Covid-19 infection (Fisher´s exact test, p = 0.0005). N95 masks and eye protection devices were available for 87% and 73%, respectively. A total of 254/502 (51%) had been vaccinated against seasonal influenza. The overall SARS-CoV-2 infection rate of german physicians from intensive care and emergency medicine was low compared to reports from other countries and settings. This finding may be explained by the fact that the German health care system was not overwhelmed by the first wave of the SARS-CoV-2 pandemic.


Assuntos
Anticorpos Antivirais/sangue , Cuidados Críticos , Médicos , /metabolismo , Adulto , Idoso , /diagnóstico , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos
4.
PLoS Pathog ; 17(4): e1009453, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33831132

RESUMO

There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these "future" viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8-17 years later. The decreased neutralization of "future" viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Coronavirus Humano 229E/genética , Coronavirus Humano 229E/imunologia , Evasão da Resposta Imune , Humanos , /imunologia
5.
Front Immunol ; 12: 629185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833755

RESUMO

The WHO declared the COVID-19 outbreak a public health emergency of international concern. The causative agent of this acute respiratory disease is a newly emerged coronavirus, named SARS-CoV-2, which originated in China in late 2019. Exposure to SARS-CoV-2 leads to multifaceted disease outcomes from asymptomatic infection to severe pneumonia, acute respiratory distress and potentially death. Understanding the host immune response is crucial for the development of interventional strategies. Humoral responses play an important role in defending viral infections and are therefore of particular interest. With the aim to resolve SARS-CoV-2-specific humoral immune responses at the epitope level, we screened clinically well-characterized sera from COVID-19 patients with mild and severe disease outcome using high-density peptide microarrays covering the entire proteome of SARS-CoV-2. Moreover, we determined the longevity of epitope-specific antibody responses in a longitudinal approach. Here we present IgG and IgA-specific epitope signatures from COVID-19 patients, which may serve as discriminating prognostic or predictive markers for disease outcome and/or could be relevant for intervention strategies.


Assuntos
/imunologia , Epitopos/imunologia , Proteoma/imunologia , /imunologia , Adulto , Anticorpos Antivirais/imunologia , Feminino , Humanos , Imunidade Humoral , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Masculino
6.
Front Immunol ; 12: 637152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833758

RESUMO

After a year of evolution of the SARS-CoV-2 epidemic, there is still no specific effective treatment for the disease. Although the majority of infected people experience mild disease, some patients develop a serious disease, especially when other pathologies concur. For this reason, it would be very convenient to find pharmacological and immunological mechanisms that help control SARS-CoV-2 infection. Since the COVID-19 and BCoV viruses are very close phylogenetically, different studies demonstrate the existence of cross-immunity as they retain shared epitopes in their structure. As a possible control measure against COVID-19, we propose the use of cow's milk immune to BCoV. Thus, the antigenic recognition of some highly conserved structures of viral proteins, particularly M and S2, by anti-BCoV antibodies present in milk would cause a total or partial inactivation of SARS-COV-2 (acting as a particular vaccine) and be addressed more easily by GALT's highly specialized antigen-presenting cells, thus helping the specific immune response.


Assuntos
Anticorpos Antivirais/imunologia , Coronavirus Bovino/imunologia , /imunologia , Animais , Bovinos
7.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33836604

RESUMO

The COVID-19 pandemic has reemphasized the need to identify safe and scalable therapeutics to slow or reverse symptoms of disease caused by newly emerging and reemerging viral pathogens. Recent clinical successes of monoclonal antibodies (mAbs) in therapy for viral infections demonstrate that mAbs offer a solution for these emerging biothreats. We have explored this with respect to Junin virus (JUNV), an arenavirus classified as a category A high-priority agent and the causative agent of Argentine hemorrhagic fever (AHF). There are currently no Food and Drug Administration-approved drugs available for preventing or treating AHF, although immune plasma from convalescent patients is used routinely to treat active infections. However, immune plasma is severely limited in quantity, highly variable in quality, and poses significant safety risks including the transmission of transfusion-borne diseases. mAbs offer a highly specific and consistently potent alternative to immune plasma that can be manufactured at large scale. We previously described a chimeric mAb, cJ199, that provided protection in a guinea pig model of AHF. To adapt this mAb to a format more suitable for clinical use, we humanized the mAb (hu199) and evaluated it in a cynomolgus monkey model of AHF with two JUNV isolates, Romero and Espindola. While untreated control animals experienced 100% lethality, all animals treated with hu199 at 6 d postinoculation (dpi) survived, and 50% of animals treated at 8 dpi survived. mAbs like hu199 may offer a safer, scalable, and more reproducible alternative to immune plasma for rare viral diseases that have epidemic potential.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Antivirais/farmacologia , Febre Hemorrágica Americana/prevenção & controle , Vírus Junin/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Cobaias , Febre Hemorrágica Americana/sangue , Humanos , Macaca fascicularis
9.
Sci Rep ; 11(1): 8021, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850202

RESUMO

At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.


Assuntos
Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Troca Materno-Fetal , /imunologia , Adulto , Feminino , Idade Gestacional , Humanos , Imunoensaio , Lactente , Recém-Nascido , Masculino , Gravidez , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , /isolamento & purificação
10.
BMC Infect Dis ; 21(1): 350, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33853532

RESUMO

BACKGROUND: The SARS-CoV-2 infection has emerged as a rapidly spreading infection. Today it is relatively easy to isolate Covid-19 symptomatic cases, while remains problematic to control the disease spread by infected but symptom-free individuals. The control of this possible path of contagion requires drastic measures of social distancing, which imply the suspension of most activities and generate economic and social issues. This study is aimed at estimating the percentage of asymptomatic SARS-CoV-2 infection in a geographic area with relatively low incidence of Covid-19. METHODS: Blood serum samples from 388 healthy volunteers were analyzed for the presence of anti-SARS-CoV-2 IgG by using an ELISA assay based on recombinant viral nucleocapsid protein. RESULTS: We found that 7 out of 388 healthy volunteers, who declared no symptoms of Covid-19, like fever, cough, fatigue etc., in the preceding 5 months, have bona fide serum anti-SARS-CoV-2 IgG, that is 1.8% of the asymptomatic population (95% confidence interval: 0.69-2.91%). CONCLUSIONS: The estimated range of asymptomatic individuals with anti-SARS-CoV-2 IgG should be between 26,565 and 112, 350. In the same geographic area, there are 4665 symptomatic diagnosed cases.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas , /epidemiologia , Adulto , Idoso , Humanos , Imunoglobulina G/sangue , Incidência , Itália/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
11.
Clin Lab ; 67(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33865257

RESUMO

BACKGROUND: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan and rapidly spread globally. The speed and scope of the spread of COVID-19 makes it urgent to define clinical characteristics, serological and radiological changes of the affected patients. METHODS: Seven patients with laboratory-confirmed COVID-19 who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University Yuedong Hospital from January 2020 to March 2020 were retrospectively enrolled and their clinical features, serological and radiological longitudinal changes were analyzed. RESULTS: Among the 7 patients, all (100%) had a clear epidemiological history. The most common symptoms were respiratory symptoms 6 (85.7%), and only 2 (28.6%) of the patients had fever at their first visit. The cohort included 4 (57.1%) common types and 3 (42.9%) severe types. Two (28.6%) common type patients developed to severe type in a short time. All of the 7 patients (100%) had abnormal liver function, normal renal function, and normal procalcitonin. The detection time of specific antibody in 7 patients was 5 - 13 days after symptoms. Before the specific antibody could be detected, the absolute value of lymphocytes decreased in 2 (28.6%) common type cases transferred to severe type cases accompanied with obvious progress in pulmonary imaging. The phenomenon of decreased albumin and elevated globulin occurred in 6 patients (85.7%). The predominant pattern of lung lesions observed was bilateral (71.4%) and mainly near the pleura at the first diagnosis. Bilateral pulmonary involvement occurred in 6 cases (85.7%) during the course of disease. In 4 cases (57.1%) with obvious pulmonary lesions, the absolute value of lymphocytes decreased, albumin decreased, and globulin increased during the course of the disease. CONCLUSIONS: Serum specific antibodies can be detected within 2 weeks of onset. Close observation of the dynamic changes of absolute value of blood lymphocytes, serum albumin, and globulin which were related to pulmonary imaging changes in patients will contribute to assessment of COVID-19.


Assuntos
/sangue , /diagnóstico por imagem , Anticorpos Antivirais/sangue , China , Febre , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Contagem de Linfócitos , Estudos Retrospectivos , Albumina Sérica Humana/análise , Soroglobulinas/análise
12.
Clin Lab ; 67(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33865266

RESUMO

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is the cause of the third pneumonia-like outbreak of coronaviruses in humans during the 21st century. The status of the host immune system is a critical factor that affects the severity and outcomes of COVID-19. In particular, antibody responses are an indicator of the anti-viral defense; so, a delayed or inappropriate induction of these responses would correlate with a defect in the viral clearance. METHODS: This is a rapid synthesis of literature investigating antibody responses in patients with the severe acute respiratory syndrome (SARS) and COVID-19. RESULTS: Lessons learned from severe acute respiratory syndrome (SARS), along with the direct evidence of antibody responses in COVID-19, pose the potentials of dynamic antibody responses for screening and prognostic purposes in COVID-19. Also, neutralizing antibodies extracted from recovered patients and monoclonal antibodies targeting cytokines offer therapeutic support for COVID-19. CONCLUSIONS: Altogether, the dynamics of antibody responses help to determine the effectiveness of treatments for COVID-19. Of note, it might be helpful for the evaluation of the efficacy of immunotherapy and vaccination - the dreams for the future of COVID-19. Further studies are necessary to investigate the possibility and efficacy of antibody extraction from animal subjects. Finally, numerous factors affect antibody response such as race, nutrition status, and virus mutations in viral infections, which need to be considered in the context of COVID-19.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , /diagnóstico , Biomarcadores/sangue , Humanos , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/virologia
14.
BMJ Open ; 11(4): e045425, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795310

RESUMO

OBJECTIVES: We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19. DESIGN: Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020. PRIMARY MEASURE: Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections. RESULTS: We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous. CONCLUSION: Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.


Assuntos
Anticorpos Antivirais/sangue , Estudos Soroepidemiológicos , /sangue , Europa (Continente)/epidemiologia , Alemanha , Grécia , Humanos , Itália , Pandemias
15.
Orv Hetil ; 162(15): 563-570, 2021 04 02.
Artigo em Húngaro | MEDLINE | ID: mdl-33798101

RESUMO

Összefoglaló. A koronavírus-betegség 2019 (COVID-19)-pandémia komoly kihívás elé állította nemcsak a mikrobiológiai laboratóriumokat, hanem az eredmények interpretálásában a klinikumban dolgozó kollégákat is. Az orvostudomány specializált világában az immunológiai és a fertozo betegségekkel kapcsolatos ismeretek az antimikrobás terápiás megoldások sikeressége, valamint a széles köru vakcináció miatt az idok folyamán számos szakterületen háttérbe szorultak, felfrissítésük sürgeto és elengedhetetlen része a pandémiával való megküzdésnek. A diagnosztikai vizsgálatok fontos eszközei a járvány megfékezésének, illetve a betegek ellátásának, azonban a vírus és az emberi szervezet interakciójának megértése elengedhetetlenül szükséges a korrekt epidemiológiai és gyógyászati véleményalkotáshoz. Jelen cikkünk az orvosi gyakorlat számára foglalja össze a súlyos akut légzoszervi szindrómát okozó koronavírus-2 (SARS-CoV-2) kimutatására, valamint az immunrendszer specifikus immunválaszának szerológiai vizsgálatára irányuló, gyakorlatban használatos módszereket, azok helyét, szerepét és értékelésük szempontjait a tudomány jelen állása szerint. Orv Hetil. 2021; 162(15): 563-570. Summary. The coronavirus disease 2019 (COVID-19) pandemic posed a serious challenge not only for microbiology laboratories, but also for the clinicians in interpretation of the results. In the specialized world of medicine, knowledge of immunological and infectious diseases has been relegated to the background in many disciplines over time due to the success of antimicrobial therapies and widespread vaccination, so updating them is an urgent and essential part of the fight against the pandemic. Diagnostic tests are important tools for controlling the epidemic and caring for patients, but understanding the interaction between the virus and the human body is essential to form a correct epidemiological and medical opinion. This paper summarizes the medical methods for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the serological testing of the specific immune response of the immune system, their place, role and criteria of their evaluation according to current scientific knowledge. Orv Hetil. 2021; 162(15): 563-570.


Assuntos
Anticorpos Antivirais , Antígenos Virais , Anticorpos Antivirais/isolamento & purificação , Antígenos Virais/isolamento & purificação , Humanos , /imunologia
18.
BMC Infect Dis ; 21(1): 341, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845787

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. METHODS: Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. RESULTS: Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model. CONCLUSIONS: Influenza virus IgM positive may be associated with decreasing in-hospital death.


Assuntos
/complicações , Mortalidade Hospitalar , Influenza Humana/complicações , Adulto , Idoso , Anticorpos Antivirais/sangue , China , Coinfecção/virologia , Comorbidade , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Front Immunol ; 12: 614436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790892

RESUMO

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of the coronavirus disease 2019 (COVID-19), which elicits a wide variety of symptoms, ranging from mild to severe, with the potential to lead to death. Although used as the standard method to screen patients for SARS-CoV-2 infection, real-time PCR has challenges in dealing with asymptomatic patients and those with an undetectable viral load. Serological tests are therefore considered potent diagnostic tools to complement real-time PCR-based diagnosis and are used for surveillance of seroprevalence in populations. However, the dynamics of the antibody response against SARS-CoV-2 currently remain to be investigated. Here, through analysis of plasma samples from 84 patients with COVID-19, we observed that the response of virus-specific antibodies against three important antigens, RBD, N and S, dynamically changed over time and reached a peak 5-8 weeks after the onset of symptoms. The antibody responses were irrespective of sex. Severe cases were found to have higher levels of antibody response, larger numbers of inflammatory cells and C-reactive protein levels. Within the mild/moderate cases, pairwise comparison indicated moderate association between anti-RBD vs. anti-N, anti-RBD vs. anti-S1S2, and anti-N vs. anti-S1S2. Furthermore, the majority of cases could achieve IgM and IgG seroconversion at 2 weeks since the disease onset. Analysis of neutralizing antibodies indicated that these responses were able to last for more than 112 days but decline significantly after the peak. In summary, our findings demonstrate the longitudinally dynamic changes in antibody responses against SARS-CoV-2, which can contribute to the knowledge of humoral immune response after SARS-CoV-2 infection and are informative for future development of vaccine and antibody-based therapies.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , /imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Pequim , China , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Domínios Proteicos/imunologia , Soroconversão , Índice de Gravidade de Doença , Centros de Atenção Terciária
20.
Science ; 372(6537)2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33795432

RESUMO

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins.


Assuntos
Anticorpos/química , Anticorpos/imunologia , Nanoestruturas , Engenharia de Proteínas , Transdução de Sinais , Angiopoietinas/química , Angiopoietinas/imunologia , Angiopoietinas/metabolismo , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Antígenos CD40/química , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Simulação por Computador , Genes Sintéticos , Humanos , Fragmentos Fc das Imunoglobulinas/química , Ativação Linfocitária , Modelos Moleculares , Ligação Proteica , Receptor TIE-2/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Linfócitos T/imunologia , Linfócitos T/fisiologia
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