Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS

Yip, Ming Shum; Cheung, Chung Yan; Li, Ping H; Bruzzone, Roberto; Peiris, JS Malik; Jaume, Martial

doi:10.1186/1753-6561-5-s1-p80

Cited by 110 publications

(143 citation statements)

References 3 publications

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“…However, development of a safe coronavirus vaccine is complicated by the possibility that such a vaccine may contribute to COVID-19 pathology. There are now multiple examples in the literature whereby a SARS-CoV-1 vaccine can have a deleterious effect in non-human recipients (Jaume et al, 2012) Wang et al, 2016;Yip et al, 2016), and SARS-CoV-1 ADE has been observed by several groups in cell culture studies (Jaume et al, 2011;Liu et al, 2019;Wan et al, 2020;Wang et al, 2014;Yang et al, 2005;Yip et al, 2014). ADE is more obvious in feline coronavirus, where it results in a shift in tropism and increase in disease severity (Huisman et al, 1998;Huisman et al, 2009;Weiss and Scott, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…The RBD is easier to produce, and is less likely to elicit antibodies against poorly neutralizing but more immunogenic epitopes. In addition, antibodydependent enhancement (ADE) contributes to the pathogenicity of feline coronaviruses (Huisman et al, 2009;Olsen et al, 1992;Weiss and Scott, 1981), and has been raised as a concern for vaccines against SARS-CoV-1 (Jaume et al, 2012;Liu et al, 2019;Luo et al, 2018;Wan et al, 2020;Wang et al, 2016;Wang et al, 2014;Yang et al, 2005;Yip et al, 2016)3. ADE contributes to the pathology of other viral diseases, notably those caused by flaviviruses, and in those cases, non-neutralizing antibodies promote more efficient ADE than those which also neutralize (Dejnirattisai et al, 2010;Halstead and O'Rourke, 1977;.…”

Section: Introductionmentioning

confidence: 99%

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The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Quinlan

Mou

Zhang

et al. 2020

Preprint

138

163

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The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV (SARS-CoV-1), a closely related coronavirus which emerged in 2002-2003, have been shown to potently neutralize SARS-CoV-1 S-protein-mediated entry, and the presence of anti-RBD antibodies correlates with neutralization in SARS-CoV-2 convalescent sera. Here we show that immunization with the SARS-CoV-2 RBD elicits a robust neutralizing antibody response in rodents, comparable to 100 µg/ml of ACE2-Ig, a potent SARS-CoV-2 entry inhibitor. Importantly, anti-sera from immunized animals did not mediate antibodydependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARS-CoV-2 could be safe and effective.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Quinlan

Mou

Zhang

et al. 2020

Preprint

138

163

View full text Add to dashboard Cite

show abstract

“…21,22 Except for one subject, and antigenically related to -229E) infectivity has been reported and can be mediated by antibodies to S protein epitopes. 15,[23][24][25] Also, studies of the S protein sequence and neutralization antigenicity suggest that serum antibodies which neutralize clinical HCoV isolates may not cross-react as well with the laboratory strains of HCoV that were used in our neutralization assays, affecting the sensitivity of the neutralization assay that was employed here. 4,6 Indeed, quasi-species of HCoV-OC43 were detected in respiratory secretions in our patients, with mutational peaks in the S1 region of the Spike protein that could lead to differences in antigenicity, 26 and lower neutralization antibody levels and response rates against laboratory-adapted strains.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus‐associated illnesses

Gorse

Donovan

Patel

2020

Journal of Medical Virology

141

152

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Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections. K E Y W O R D Santibody, coronavirus, immunity, neutralization, respiratory illness

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“…16,17 It was previously shown that the SARS-CoV-1 virus (SARS-CoV) can enter macrophages via a suboptimal antibody-mediated pathway and it can replicate in these cells. 18 Viral-Track, which allows unsupervised detection of viral RNA in single-cell RNA-seq datasets, also found evidence of SARS-COV-2 infection in monocytes/macrophages in severe patients. 19 In addition, viral antigens were also detected in macrophages infiltrated into the alveolar interstitium and cavities of SARS-CoV-2-infected hACE2-expressing mice.…”

Section: Ade Can Explain Characteristics Of Severe Covid-19mentioning

confidence: 94%

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

Zheng¹,

Liu

2020

Journal of Medical Virology

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Coronavirus disease 2019 (COVID-19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID-19.After a systematical review of the literature, we propose that cross-reactive antibodies associated with antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV-2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID-19. K E Y W O R D S ADE, antibody-dependent enhancement, coronavirus, cross-reactive antibody, cytokine storm, immunity, mTOR inhibitors, rapamycin How to cite this article: Zheng Y, Li R, Liu S. Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines.

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Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS

Cited by 110 publications

References 3 publications

The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus‐associated illnesses

Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

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