Epitope Diversity and SARS-CoV-2 Variants Neutralizing Capacity of SARS-CoV-2 Hyperimmune Intravenous Immunoglobulins for Treatment of COVID-19

2021 ◽  
Author(s):  
Juanjie Tang ◽  
Youri Lee ◽  
Supriya Ravichandran ◽  
Gabrielle Grubbs ◽  
Chang Huang ◽  
...  
2021 ◽  
Author(s):  
Juanjie Tang ◽  
Your Lee ◽  
Supriya Ravichandran ◽  
Gabrielle Grubbs ◽  
Chang Huang ◽  
...  

Hyperimmune immunoglobulin (hCoV-2IG) preparations generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in several clinical trials of hospitalized COVID-19 patients. Here we explored the antibody epitope repertoire, antibody binding and virus neutralizing capacity of six hCoV-2IG batches as well as nine convalescent plasma (CP) lots against SARS-CoV-2 and emerging variants of concern (VOC). The Gene-Fragment Phage display library spanning the SARS-CoV-2 spike demonstrated broad recognition of multiple antigenic sites spanning the entire spike including NTD, RBD, S1/S2 cleavage site, S2-fusion peptide and S2-heptad repeat regions. Antibody binding to the immunodominant epitopes was higher for hCoV-2IG than CP, with predominant binding to the fusion peptide. In the pseudovirus neutralization assay (PsVNA) and in the wild-type SARS-CoV-2 PRNT assay, hCoV-2IG lots showed higher titers against the WA-1 strain compared with CP. Neutralization of SARS-CoV-2 VOCs from around the globe were reduced to different levels by hCoV-2IG lots. The most significant loss of neutralizing activity was seen against the B.1.351 (9-fold) followed by P.1 (3.5-fold), with minimal loss of activity against the B.1.17 and B.1.429 (<2-fold). Again, the CP showed more pronounced loss of cross-neutralization against the VOCs compared with hCoV-2IG. Significant reduction of hCoV-2IG binding was observed to the RBD-E484K followed by RBD-N501Y and minimal loss of binding to RBD-K417N compared with unmutated RBD. This study suggests that post-exposure treatment with hCoV-2IG is preferable to CP. In countries with co-circulating SARS-CoV-2 variants, identifying the infecting virus strain could inform optimal treatments, but would likely require administration of higher volumes or repeated infusions of hCOV-2IG or CP, in patients infected with the emerging SARS-CoV-2 variants.


2009 ◽  
Vol 29 (02) ◽  
pp. 155-157 ◽  
Author(s):  
H. Hauch ◽  
J. Rischewski ◽  
U. Kordes ◽  
J. Schneppenheim ◽  
R. Schneppenheim ◽  
...  

SummaryInhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.


1997 ◽  
Vol 78 (02) ◽  
pp. 969-970 ◽  
Author(s):  
Gilles Pernod ◽  
Josiane Arvieux ◽  
Patrick H Carpentier ◽  
Pascal Mossuz ◽  
Jean Luc Bosson ◽  
...  

Author(s):  
Maria Gogou ◽  
Efimia Papadopoulou-Alataki ◽  
Martha Spilioti ◽  
Sofia Alataki ◽  
Athanasios Evangeliou

2016 ◽  
Vol 5 (04) ◽  
pp. 4524
Author(s):  
Abdullah Shaikh Farooque ◽  
Md. Azharuddin Ismail Atar*

Medicinal plants are being widely used, either as single drug or in combination in health care delivery system. Indian Sarsaparilla, Hemidesmus indicus (Family: Asclepiadaceae) is a commonly known Indian Medicinal Plant, which is widely recognized in traditional systems of Medicine. It contains various phytoconstituents belonging to the category glycosides, flavonoids, tannins, sterols and volatile oils. It has been reported as useful in biliousness, blood diseases, dysentery, diarrhea, respiratory disorders, skin diseases, syphilis, fever, leprosy, leucoderma, leucorrhoea, itching, bronchitis, asthma, eye diseases, epileptic fits in children, kidney and urinary disorders, loss of appetite, burning sensation, dyspepsia, nutritional disorders, ulcer and rheumatism. Several studies are being carried towards its activities like analgesic, anti-inflammatory, antiulcer, hepatoprotective, antioxidant and helicobactericidal properties. In our study we have evaluated antacid activity of sariva (Anantmool) by using In-Vitro method, i.e. ANC (Acid Neutralizing Capacity). This evaluation was done by comparing the ANC of sariva macerated & powdered drug with water as blank & standard drug i.e. NaHCO3. Based on this In-Vitro experiment, we can conclude that, the macerated & powdered drug of sariva (Anantmool) evaluated in this study, varied in potency as measured in terms of their ANC. These results having ** i.e. P < 0.01 & Passed the normality test. However, the present study being in-vitro, the effects of antacid may vary In-Vitro; individual variations also contribute to the ultimate effectiveness of as antacid.        


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