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1.
J Immunol Res ; 2020: 9465398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134398

RESUMO

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Mapeamento de Epitopos , Imunoglobulinas/isolamento & purificação , Pneumonia Viral/terapia , Administração Intranasal , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Galinhas , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Estudos de Viabilidade , Humanos , Imunização Passiva/métodos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/imunologia
2.
Pediatr Infect Dis J ; 39(11): e366-e367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021596

RESUMO

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulinas/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Pneumonia Viral/imunologia , Proteínas Virais/imunologia , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunidade Humoral , Imunoglobulinas/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia
3.
mBio ; 11(5)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067385

RESUMO

In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms.IMPORTANCE While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.


Assuntos
Betacoronavirus/imunologia , Convalescença , Infecções por Coronavirus/imunologia , Imunidade Humoral , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções por Coronavirus/sangue , Reações Cruzadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Glicoproteína da Espícula de Coronavírus/química , Adulto Jovem
4.
Front Immunol ; 11: 2130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013898

RESUMO

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.


Assuntos
Betacoronavirus/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Animais , Anticorpos Facilitadores/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunização Passiva , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Atenuadas/imunologia , Vacinas de DNA/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades/imunologia
5.
Sci Immunol ; 5(52)2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033172

RESUMO

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Domínios Proteicos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Betacoronavirus/genética , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/virologia , Reações Cruzadas , Teste em Amostras de Sangue Seco , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/química
6.
Sci Rep ; 10(1): 16561, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024213

RESUMO

As the Coronavirus Disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses (CoVs). The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Proteínas do Nucleocapsídeo/imunologia , Pneumonia Viral/diagnóstico , Soroconversão , Testes Sorológicos/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Betacoronavirus/genética , Estudos de Coortes , Infecções por Coronavirus/virologia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Adulto Jovem
8.
PLoS One ; 15(10): e0241471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112930

RESUMO

Anecdotal evidence showed a negative correlation between Bacille Calmette-Guérin (BCG) vaccination and incidence of COVID-19. Incidence of the disease in children is much lower than in adults. It is hypothesized that BCG and other childhood vaccinations may provide some protection against SARS-CoV-2 infection through trained or adaptive immune responses. Here, we tested whether BCG, Pneumococcal, Rotavirus, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus influenzae, Hepatitis B, Meningococcal, Measles, Mumps, and Rubella vaccines provide cross-reactive neutralizing antibodies against SARS-CoV-2 in BALB/c mice. Results indicated that none of these vaccines provided antibodies capable of neutralizing SARS-CoV-2 up to seven weeks post vaccination. We conclude that if such vaccines have any role in COVID-19 immunity, this role is not antibody-mediated.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Infecções por Coronavirus/imunologia , Reações Cruzadas , Feminino , Humanos , Soros Imunes/imunologia , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Testes de Neutralização , Pneumonia Viral/imunologia , Vacinação , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Adulto Jovem
9.
Toxicon ; 188: 150-158, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33127373

RESUMO

While snakebite is a severe problem for several countries throughout the world the Indian subcontinent has witnessed the highest global incidence of snakebite which represents an occupational health hazard. Belonging to the family Elapidae, the Indian spectacled cobra (Naja naja), is one of the members of the "Big Four" venomous snakes found throughout the Indian subcontinent. Indian monocled cobra Naja kaouthia is prevalent in eastern and north-eastern India as well as in Bangladesh, Nepal, and Bhutan. Species-specific and geographical differences in venom composition of two major Indian cobras (N. naja vs. N. kaouthia) may limit the effectiveness of antivenom treatment. Therefore, exploring the venom proteomes of N. naja and N. kaouthia from different geographical locales of the Indian subcontinent, and the effect of this variation on antivenom efficacy is warranted. Proteomic analyses have demonstrated that although eastern Indian N. naja and N. kaouthia venoms have similarities, species-specific and geographical variation is evident by differences in their venom toxicity values and pathobiological effects in experimental animals. This is the major reason as to why a polyvalent antivenom against N. naja venom exhibited only partial neutralization of enzymatic activity and immunological cross-reactivity against cobra venoms from other regions of India. This suggests that addition of polyclonal antibodies against N. kaouthia venom to polyantivenom, or preparation/administration of region-specific polyantivenom will provide better treatment of cobra bites in the Indian subcontinent.


Assuntos
Venenos Elapídicos , Elapidae , Animais , Antivenenos , Bangladesh , Reações Cruzadas , Geografia , Índia , Proteoma , Mordeduras de Serpentes
10.
PLoS One ; 15(10): e0238609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112881

RESUMO

INTRODUCTION: Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. METHODOLOGY AND RESULTS: 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). CONCLUSIONS: As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Encefalite Japonesa (Espécie)/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Especificidade de Anticorpos , Criança , Sequência Conservada , Reações Cruzadas , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/virologia , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Feminino , Voluntários Saudáveis , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Sorogrupo , Sri Lanka/epidemiologia , Vacinação , Proteínas Virais/genética , Proteínas Virais/imunologia , Adulto Jovem
11.
Nat Rev Immunol ; 20(11): 709-713, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33024281

RESUMO

Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronaviridae/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Coronaviridae/efeitos dos fármacos , Coronaviridae/imunologia , Infecções por Coronaviridae/epidemiologia , Infecções por Coronaviridae/imunologia , Infecções por Coronaviridae/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Humanos , Imunidade Coletiva/efeitos dos fármacos , Memória Imunológica , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Rhinovirus/efeitos dos fármacos , Rhinovirus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
13.
Nat Commun ; 11(1): 5278, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077712

RESUMO

There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the ß-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.


Assuntos
Anticorpos Antivirais/administração & dosagem , Complicações Infecciosas na Gravidez/prevenção & controle , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Antivirais/imunologia , Afinidade de Anticorpos , Anticorpos Facilitadores , Reações Cruzadas , Epitopos/química , Epitopos/genética , Epitopos/imunologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Zika virus/química , Zika virus/genética , Infecção por Zika virus/congênito , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
14.
Exp Parasitol ; 218: 107999, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32956649

RESUMO

Angiostrongylus cantonensis is the main causative agent of eosinophilic meningoencephalitis (EoM) in humans. Molecular diagnostic methods are essential since the identification of larvae in cerebrospinal fluid (CSF) is extremely rare. To date, the detection of a 31 kDa antigen by Western blotting has been the primary immunodiagnostic method for EoM caused by A. cantonensis. However, cross-reactivity with other parasites has been observed. Therefore, we conducted a comparative analysis using sera from individuals with angiostrongyliasis. We also characterized proteins isolated from different cellular sources of A. cantonensis, Toxocara canis, Schistosoma mansoni, and Strongyloides stercoralis with mass spectrometry. A total of 115 cross-reactive proteins were identified. Three of these proteins, heat shock protein, an intermediate filament protein, and galectin 1, represent potential markers for cross-reactivity. In addition, synthetic peptides were generated from previously identified diagnostic targets and tested against sera from individuals infected with several other parasites. As a result, two other markers of cross-reactivity were identified: peptide #4 derived from the 14-3-3 protein and peptide #12 derived from the Lec-5 protein. In contrast, 34 proteins were exclusively present in the Angiostrongylus extracts and represent promising diagnostic molecules for specific identification of A. cantonensis infection. In particular, cytochrome oxidase subunit I is of great interest as a possible immunodiagnostic target for angiostrongyliasis.


Assuntos
Angiostrongylus cantonensis/imunologia , Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Meningoencefalite/diagnóstico , Meningoencefalite/parasitologia , Infecções por Strongylida/diagnóstico , Sequência de Aminoácidos , Angiostrongylus cantonensis/química , Animais , Antígenos de Helmintos/sangue , Antígenos de Helmintos/química , Antígenos de Helmintos/isolamento & purificação , Western Blotting , Sequência Conservada , Reações Cruzadas , Eletroforese , Eletroforese em Gel Bidimensional , Proteínas de Helminto/química , Proteínas de Helminto/isolamento & purificação , Humanos , Imunoensaio , Testes Imunológicos , Espectrometria de Massas , Meningoencefalite/imunologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia
16.
Emerg Microbes Infect ; 9(1): 2013-2019, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32867625

RESUMO

COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Pneumonia Viral/veterinária , Animais , Gatos , China , Infecções por Coronavirus/epidemiologia , Coronavirus Felino/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Proteínas do Nucleocapsídeo/imunologia , Pneumonia Viral/epidemiologia , Glicoproteína da Espícula de Coronavírus/imunologia
17.
mSphere ; 5(5)2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878931

RESUMO

The novel coronavirus, SARS-coronavirus (CoV)-2 (SARS-CoV-2), has caused over 17 million infections in just a few months, with disease manifestations ranging from largely asymptomatic infection to critically severe disease. The remarkable spread and unpredictable disease outcomes continue to challenge management of this infection. Among the hypotheses to explain the heterogeneity of symptoms is the possibility that exposure to other coronaviruses (CoVs), or overall higher capability to develop immunity against respiratory pathogens, may influence the evolution of immunity to SARS-CoV-2. Thus, we profiled the immune response across multiple coronavirus receptor binding domains (RBDs), respiratory viruses, and SARS-CoV-2, to determine whether heterologous immunity to other CoV-RBDs or other infections influenced the evolution of the SARS-CoV-2 humoral immune response. Overall changes in subclass, isotype, and Fc-receptor binding were profiled broadly across a cohort of 43 individuals against different coronaviruses-RBDs of SARS-CoV-2 and the more common HKU1 and NL63 viruses. We found rapid functional evolution of responses to SARS-CoV-2 over time, along with broad but relatively more time-invariant responses to the more common CoVs. Moreover, there was little evidence of correlation between SARS-CoV-2 responses and HKU1, NL63, and respiratory infection (influenza and respiratory syncytial virus) responses. These findings suggest that common viral infections including common CoV immunity, targeting the receptor binding domain involved in viral infection, do not appear to influence the rapid functional evolution of SARS-CoV-2 immunity, and thus should not impact diagnostics or shape vaccine-induced immunity.IMPORTANCE A critical step to ending the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ability to detect, diagnose, and understand why some individuals develop mild and others develop severe disease. For example, defining the early evolutionary patterns of humoral immunity to SARS-CoV-2, and whether prevalent coronaviruses or other common infections influence the evolution of immunity, remains poorly understood but could inform diagnostic and vaccine development. Here, we deeply profiled the evolution of SARS-CoV-2 immunity, and how it is influenced by other coinfections. Our data suggest an early and rapid rise in functional humoral immunity in the first 2 weeks of infection across antigen-specific targets, which is negligibly influenced by cross-reactivity to additional common coronaviruses or common respiratory infections. These data suggest that preexisting receptor binding domain-specific immunity does not influence or bias the evolution of immunity to SARS-CoV-2 and should have negligible influence on shaping diagnostic or vaccine-induced immunity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Heteróloga , Imunidade Humoral , Pneumonia Viral/imunologia , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Reações Cruzadas , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia
18.
mBio ; 11(5)2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978311

RESUMO

The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCE The recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key issues are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and postinfection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study results also suggest that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.


Assuntos
Linfócitos B/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulina G/imunologia , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Antivirais/imunologia , Linfócitos B/virologia , Convalescença , Reações Cruzadas , Feminino , Voluntários Saudáveis , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Domínios e Motivos de Interação entre Proteínas , Subunidades Proteicas , Glicoproteína da Espícula de Coronavírus/química
19.
Emerg Microbes Infect ; 9(1): 2157-2168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940547

RESUMO

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4-99.0%), Abbott Test (94.0%, 89.1-96.8%), Wondfo Test (91.4%, 85.8-94.9%), ASK Test (97.4%, 93.4-99.0%), and Dynamiker Test (90.1%, 84.3-94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3-99.7%) for the Roche Test, 97.9% (95% CI, 94.8-99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1-100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Imunoensaio/métodos , Medições Luminescentes/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Feminino , Humanos , Imunoensaio/normas , Medições Luminescentes/normas , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Reprodutibilidade dos Testes , Soroconversão , Testes Sorológicos , Índice de Gravidade de Doença , Taiwan/epidemiologia
20.
Signal Transduct Target Ther ; 5(1): 212, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963228

RESUMO

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


Assuntos
Anticorpos Monoclonais/química , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Epitopos/química , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Modelos Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Secundária de Proteína , Receptores Virais/química , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vírion/imunologia , Vírion/ultraestrutura
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