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1.
Euro Surveill ; 25(28)2020 07.
Article in English | MEDLINE | ID: covidwho-647504

ABSTRACT

BackgroundA novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.AimThe cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.MethodsThe SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.ResultsAn immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.ConclusionThe cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Animals , Betacoronavirus/genetics , Blotting, Western , COS Cells , Chlorocebus aethiops , Conserved Sequence , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay/methods , Fluorescent Antibody Technique/methods , Genome, Viral , Mice , Pandemics , Peptidyl-Dipeptidase A/immunology , Plasmids , Pneumonia, Viral/genetics , Recombinant Proteins/immunology , SARS Virus/genetics , Sequence Alignment , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Transfection , Vero Cells , Virus Integration
2.
Nat Commun ; 11(1): 4198, 2020 08 21.
Article in English | MEDLINE | ID: covidwho-724360

ABSTRACT

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Immunoglobulin A/immunology , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/metabolism , Chlorocebus aethiops , Cross Reactions , Epitopes , HEK293 Cells , Humans , Immunoglobulin A/metabolism , Immunoglobulin A, Secretory/immunology , Immunoglobulin A, Secretory/metabolism , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Models, Molecular , Mutation , Protein Binding , Protein Interaction Domains and Motifs , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
4.
Rev. Hosp. Ital. B. Aires (2004) ; 40(2): 63-75, jun. 2020. graf, ilus, tab
Article in Spanish | LILACS (Americas) | ID: covidwho-679089

ABSTRACT

El objetivo de este artículo es proporcionar una guía que sirva para la interpretación y seguimiento de los esfuerzos que se están desarrollando en todo el mundo con el objetivo de obtener una vacuna que pueda generar inmunidad contra el nuevo coronavirus SARS-CoV-2 de 2019, el agente causante de la enfermedad por coronavirus denominada COVID-19. Cinco meses después de haber sido detectada la enfermedad, ya hay 102 vacunas en distintos estadios de desarrollo, registradas por la Organización Mundial de la Salud (OMS), correspondientes a 8 plataformas vacunales con diferentes estrategias, y todos los días aparecen nuevas. Esto representará un enorme desafío de organismos internacionales, para la evaluación, comparación y selección de aquellas que cumplan con los criterios regulatorios indispensables de seguridad y eficacia y que, por otro lado, puedan ser producidas en cantidades suficientes para abastecer la demanda mundial. (AU)


The objective of this article is to provide a guide to help the interpretation and monitoring the efforts that are being carried out worldwide to obtain a vaccine that will be able to generate immunity against the new 2019 SARS-CoV-2 coronavirus, the viral agent causes the disease named COVID-19. Five months after the disease was detected, there are already 102 vaccines at different stages of development, registered by World Health Organization (WHO), corresponding to 8 vaccination platforms base on different strategies, and every day new ones appear. This will represent a huge challenge for international organizations, to evaluate, compare and selects those that will meet the essential regulatory criteria of safety and efficacy and that, would be able to be produced in enough quantities to supply the worldwide demand. Key words: SARS-Cov-2 vaccine, vaccine platform, COVID-19 strategy, attenuated virus, viral vector, viral proteins, viral DNA, viral RNA, nucleic acids, viral like particles, WHO. (AU)


Subject(s)
Humans , Male , Female , Coronavirus Infections/therapy , SARS Virus/immunology , Pneumonia, Viral/therapy , DNA/therapeutic use , RNA/therapeutic use , Vaccines/therapeutic use , Nucleic Acids/therapeutic use , Protein S/immunology , Coronavirus Infections/virology , SARS Virus/physiology , SARS Virus/genetics , Disease Vectors
5.
EBioMedicine ; 58: 102890, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-666030

ABSTRACT

BACKGROUND: The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined. METHODS: Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies. FINDINGS: We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice. INTERPRETATION: Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses. FUNDING: This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Cross Reactions , SARS Virus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibody Specificity , Betacoronavirus/genetics , CHO Cells , Cell Line, Tumor , Cricetinae , Cricetulus , Female , Humans , Mice , Mice, Inbred BALB C , SARS Virus/genetics , Sequence Homology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
6.
Nature ; 584(7821): 443-449, 2020 08.
Article in English | MEDLINE | ID: covidwho-647154

ABSTRACT

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-24. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein5, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (SRBD) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the SRBD, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Animals , Antibodies, Monoclonal/immunology , Betacoronavirus/chemistry , Binding, Competitive , Cell Line , Cross Reactions , Disease Models, Animal , Epitopes, B-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/immunology , Female , Humans , Macaca mulatta , Male , Mice , Middle Aged , Neutralization Tests , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pre-Exposure Prophylaxis , SARS Virus/chemistry , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
7.
Nature ; 584(7821): 353-363, 2020 08.
Article in English | MEDLINE | ID: covidwho-643609

ABSTRACT

Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies-regardless of what virus is the causative agent-it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.


Subject(s)
Antibodies, Viral/adverse effects , Antibodies, Viral/immunology , Antibody-Dependent Enhancement/immunology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Animals , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Coronavirus Infections/prevention & control , Dengue Virus/immunology , Disease Models, Animal , HEK293 Cells , Humans , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/immunology , Macaca mulatta , Mice , Middle East Respiratory Syndrome Coronavirus/immunology , Orthomyxoviridae/immunology , Pandemics , Rats , SARS Virus/immunology , Viral Vaccines/adverse effects , Viral Vaccines/immunology
8.
Immunity ; 53(2): 248-263, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-643222

ABSTRACT

A key goal to controlling coronavirus disease 2019 (COVID-19) is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, common cold coronaviruses, and SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Pneumonia, Viral/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/immunology , Adaptive Immunity/immunology , Animals , Betacoronavirus/pathogenicity , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Severe Acute Respiratory Syndrome/prevention & control , Viral Vaccines/immunology
9.
Immunol Rev ; 296(1): 205-219, 2020 07.
Article in English | MEDLINE | ID: covidwho-641222

ABSTRACT

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Disease Resistance/genetics , Genetic Predisposition to Disease , Host-Pathogen Interactions/genetics , Pneumonia, Viral/immunology , Animals , Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , SARS Virus/immunology , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology
10.
Cell ; 182(1): 7-9, 2020 07 09.
Article in English | MEDLINE | ID: covidwho-639736

ABSTRACT

The emergence of SARS-CoV-2 has driven a global research effort to identify medical countermeasures at an unprecedented pace. In this issue of Cell, Cao et al. identify thousands of SARS-CoV-2 neutralizing antibodies from convalescent donors. The authors improve our understanding of immunity against the coronavirus spike glycoprotein and detail novel pathways to rapidly identify and characterize protective monoclonal antibodies.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , SARS Virus/immunology , Antibodies, Viral , Betacoronavirus , Humans
13.
Cell ; 182(3): 722-733.e11, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-628738

ABSTRACT

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS Virus/immunology , Universal Design , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/chemistry , Cell Line, Tumor , Chlorocebus aethiops , Coronavirus Infections/virology , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus/chemistry , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Protein Binding , Protein Interaction Domains and Motifs/immunology , Receptors, Virus/metabolism , SARS Virus/chemistry , Sf9 Cells , Specific Pathogen-Free Organisms , Spodoptera , Transfection , Vaccination/methods , Vero Cells , Viral Vaccines
14.
Int Immunopharmacol ; 86: 106740, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-614079

ABSTRACT

BACKGROUND: There is no vaccine or specific antiviral treatment for HCoVs infection. The use of type I interferons for coronavirus is still under great debate in clinical practice. MATERIALS AND METHODS: A literature search of all relevant studies published on PubMed, Cochrane library, Web of Science database, Science Direct, Wanfang Data, and China National Knowledge Infrastructure (CNKI) until February 2020 was performed. RESULTS: Of the 1081 identified articles, only 15 studies were included in the final analysis. Comorbidities and delay in diagnosis were significantly associated with case mortality. Type I interferons seem to improve respiratory distress, relieve lung abnormalities, present better saturation, reduce needs for supplemental oxygen support. Type I interferons seem to be well tolerated, and don't increase life threating adverse effects. Data on IFNs in HCoVs are limited, heterogenous and mainly observational. CONCLUSIONS: Current data do not allow making regarding robust commendations for the use of IFNs in HCoVs in general or in specific subtype. But we still recommend type I interferons serving as first-line antivirals in HCoVs infections within local protocols, and interferons may be adopted to the treatments of the SARS-CoV-2 as well. Well-designed large-scale prospective randomized control trials are greatly needed to provide more robust evidence on this topic.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Interferon Type I/administration & dosage , Pneumonia, Viral/drug therapy , Antiviral Agents/adverse effects , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Humans , Interferon Type I/adverse effects , Middle East Respiratory Syndrome Coronavirus , Observational Studies as Topic , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
15.
Cell ; 182(4): 828-842.e16, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-612079

ABSTRACT

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.


Subject(s)
Antibodies, Neutralizing/chemistry , Betacoronavirus/chemistry , Coronavirus Infections/immunology , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin G/chemistry , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/immunology , Antibodies, Viral/isolation & purification , Betacoronavirus/immunology , Coronavirus Infections/blood , Coronavirus Infections/therapy , Cross Reactions , Cryoelectron Microscopy , Epitope Mapping , Epitopes , Humans , Immunization, Passive , Immunoglobulin Fab Fragments/blood , Immunoglobulin Fab Fragments/isolation & purification , Immunoglobulin Fab Fragments/ultrastructure , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Immunoglobulin G/ultrastructure , Middle East Respiratory Syndrome Coronavirus/chemistry , Middle East Respiratory Syndrome Coronavirus/immunology , Models, Molecular , Pandemics , Pneumonia, Viral/blood , SARS Virus/chemistry , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology
16.
Elife ; 92020 06 23.
Article in English | MEDLINE | ID: covidwho-611846

ABSTRACT

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/therapy , Immunization, Passive , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Antibodies, Monoclonal , Antibodies, Viral , Betacoronavirus/immunology , Broadly Neutralizing Antibodies/immunology , Humans , Pandemics , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/chemistry
18.
Paediatr Respir Rev ; 35: 43-49, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-611163

ABSTRACT

There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccines, DNA/therapeutic use , Vaccines, Synthetic/therapeutic use , Viral Vaccines/therapeutic use , Clinical Trials as Topic , Coronavirus Infections/immunology , Drug Development , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , Vaccines, DNA/immunology , Vaccines, Synthetic/immunology , Viral Vaccines/immunology
19.
J Clin Virol ; 129: 104521, 2020 08.
Article in English | MEDLINE | ID: covidwho-610625

ABSTRACT

BACKGROUND: Knowledge of the COVID-19 epidemic extent and the level of herd immunity is urgently needed to help manage this pandemic. METHODS: We used a panel of 167 samples (77 pre-epidemic and 90 COVID-19 seroconverters) and SARS-CoV1, SARS-CoV2 and MERS-CoV Spike and/or Nucleopcapsid (NC) proteins to develop a high throughput multiplex screening assay to detect IgG antibodies in human plasma. Assay performances were determined by ROC curves analysis. A subset of the COVID-19+ samples (n = 36) were also tested by a commercial NC-based ELISA test and the results compared with those of the novel assay. RESULTS: On samples collected ≥14 days after symptoms onset, the accuracy of the assay is 100 % (95 % CI: 100-100) for the Spike antigen and 99.9 % (95 % CI:99.7-100) for NC. By logistic regression, we estimated that 50 % of the patients have seroconverted at 5.7 ± 1.6; 5.7 ± 1.8 and 7.9 ± 1.0 days after symptoms onset against Spike, NC or both antigens, respectively and all have seroconverted two weeks after symptoms onset. IgG titration in a subset of samples showed that early phase samples present lower IgG titers than those from later phase. IgG to SARS-CoV2 NC cross-reacted at 100 % with SARS-CoV1 NC. Twenty-nine of the 36 (80.5 %) samples tested were positive by the commercial ELISA while 31/36 (86.1 %) were positive by the novel assay. CONCLUSIONS: Our assay is highly sensitive and specific for the detection of IgG antibodies to SARS-CoV2 proteins, suitable for high throughput epidemiological surveys. The novel assay is more sensitive than a commercial ELISA.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Immunoglobulin G/blood , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , Serologic Tests/methods , Adult , Aged , Aged, 80 and over , Antigens, Viral/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Nucleocapsid Proteins/immunology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , ROC Curve , Sensitivity and Specificity , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/immunology , Time Factors
20.
J Phys Chem B ; 124(28): 5907-5912, 2020 07 16.
Article in English | MEDLINE | ID: covidwho-604761

ABSTRACT

The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.


Subject(s)
Betacoronavirus , SARS Virus , Spike Glycoprotein, Coronavirus/chemistry , Antibodies, Viral/chemistry , Betacoronavirus/chemistry , Binding Sites , Humans , Molecular Dynamics Simulation , Peptidyl-Dipeptidase A/chemistry , Protein Binding , SARS Virus/chemistry , SARS Virus/immunology , Static Electricity
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