Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19

Coish, Jeremia M.

doi:10.1016/j.micinf.2020.06.006

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…Future studies are needed to understand the significance of these observations. It is possible that high‐titer–binding antibodies with low neutralization potential lead to antibody‐dependent enhancement, suggesting that selecting convalescent plasma units based on high binding activity alone may cause harm 14 . Similarly, future studies are needed to determine if developing high‐titer–binding antibodies with low neutralization potential is a poor prognostic sign.…”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 neutralization and serology testing of COVID‐19 convalescent plasma from donors with nonsevere disease

et al. 2020

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Background: The transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention of COVID-19, but donors with a history of nonsevere disease are serologically heterogenous. The relationship between SARS-Cov-2 antigen-binding activity and neutralization activity in this population of donors has not been defined. Study Design and Methods: Convalescent plasma units from 47 individuals with a history of nonsevere COVID-19 were assessed for antigen-binding activity of using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. These results were compared with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. Results: Positive correlations of varying strength (Spearman r = 0.37-0.52) between antigen binding and viral neutralization were identified. Donors age 48 to 75 years had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75%-82%) for those with the highest levels of neutralization. Conclusion: The strength of the relationship between antigen-binding activity and neutralization varies depending on the clinical assay used. Units in the highest tertile of binding activity for each assay are predominantly comprised of those with the greatest neutralization activity.

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Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 neutralization and serology testing of COVID‐19 convalescent plasma from donors with nonsevere disease

et al. 2020

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“…One such interaction demonstrated with diverse viral families, including Coronaviridae is ADE 44,45,46 . However, the importance of ADE phenomenon, whereby a previous immune response could render an individual more susceptible to a Cov-2 reinfection, remains undetermined 47,21 . Another potential unwanted outcome associated with anti-SARS-CoV-2 antibodies is severe acute lung injury mediated by IgG Fc-dependent macrophage recruitment in productively infected lungs, thereby skewing inflammation-resolving response 22 .…”

Section: Discussionmentioning

confidence: 99%

High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

Vanhove¹,

Duvaux²,

Rousse³

et al. 2020

Preprint

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Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Heterologous polyclonal antibodies of animal origin have been used to fight against infectious agents and are a possible alternative to the use of CP in SARS-CoV-2 disease. However, heterologous polyclonal antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrate epitopes, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the Gal alpha1,3-galactose (a-Gal), ultimately forming immune complexes and potentially leading to serum sickness or allergy. To circumvent these drawbacks, we engineered animals lacking the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) and alpha1,3-galactosyltransferase (GGTA1) enzymes to produce glyco-humanized polyclonal antibodies (GH-pAb) lacking Neu5Gc and a-Gal epitopes. We also found that these IgG Fc domains fail to interact with human Fc receptors and thereby should confer the safety advantage to avoiding macrophage dependent exacerbated inflammatory responses or elicit antibody-dependent enhancement (ADE), two drawbacks possibly associated with antibody responses against SARS-CoV-2. Therefore, we immunized CMAH/GGTA1 double knockout (DKO) pigs with the SARS-CoV-2 spike receptor binding domain (RBD) domain to elicit neutralizing antibodies. Animals rapidly developed hyperimmune sera with end-titers binding dilutions over one to a million and end-titers neutralizing dilutions of 1:10,000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized Spike/ACE-2 interaction at a concentration < 1microgram/mL and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. These data and the accumulating safety advantages of using glyco-humanized swine antibodies in humans warrant clinical assessment of XAV-19 to fight against COVID-19.

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“…[69] If the accelerated vaccine development in this pandemic will not fulfill the expectation for whatever reasons we will face public trust attrition in research and in public health overall decisions. [69] Thus, ADE or any other immunological issues should have full consideration from the scientific community for any SARS-CoV-2 vaccine [70][71][72] and the pace for vaccine development should follow the knowledge accumulation in this type of disease without cutting any research corners.…”

Section: Stability Of Viral Epitopesmentioning

confidence: 99%

The bumpy road to achieve herd immunity in COVID-19

Neagu

2020

Journal of Immunoassay and Immunochemistry

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Herd immunity is a form of indirect protection that is offered to the community when a large proportion of individuals contained in the community are immune to a certain infection. This immunity can be due to vaccination or to the recovery postdisease. Effective herd immunity in SARS-CoV-2 infection has several hurdles upon achievement. Herd immunity cannot be obtained concomitantly in many geographical areas because the areas have different population density and the societal measures to contain the spreading are different. A proportion of 50-66% of the population needs to be immunized naturally or artificially in this SARS-Cov2 pandemic and this percentage is not easily achievable. The duration of herd immunity is another issue while information on the long-term immune response against SARS-CoV2 is yet scarce. Epitope stability, another issue to be solved when achieving herd immunity, is important. Mutation in the viral structure will call upon other sets of neutralizing antibodies and hence for other herd immunity type installment. The societal tactics to achieve the much-needed herd immunity should be developed keeping in mind the welfare of the population. Without being exhaustive, throughout our paper we will elaborate on each of the hurdles encountered in developing herd immunity to SARS-Cov2 infection.

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Out of the frying pan and into the fire? Due diligence warranted for ADE in COVID-19

Cited by 19 publications

References 25 publications

SARS‐CoV‐2 neutralization and serology testing of COVID‐19 convalescent plasma from donors with nonsevere disease

SARS‐CoV‐2 neutralization and serology testing of COVID‐19 convalescent plasma from donors with nonsevere disease

High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

The bumpy road to achieve herd immunity in COVID-19

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