Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors

Mor, Michael; Werbner, Michal; Alter, Joel; Safra, Modi; Chomsky, Elad; Lee, Jamie C.; Hada-Neeman, Smadar; Polonsky, Ksenia; Nowell, Cameron J.; Clark, Alex E.; Roitburd-Berman, Anna; Ben-Shalom, Noam; Navon, Michal; Rafael, Dor; Sharim, Hila; Kiner, Evgeny; Griffis, Eric R.; Gershoni, Jonathan M.; Kobiler, Oren; Leibel, Sandra L.; Zimhony, Oren; Carlin, Aaron F.; Yaari, Gur; Dessau, Moshe; Gal-Tanamy, Meital; Hagin, David; Croker, Ben A.; Freund, Natalia T.

doi:10.1371/journal.ppat.1009165

Cited by 43 publications

(43 citation statements)

References 46 publications

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“…3E). Conspicuously, many of the most mutated variable (VH) genes in plasmablasts and memory B cells from COVID-19 patients and vaccinated individuals were from VH gene segments previously implicated in anti-SARS-CoV-2 responses (Brouwer et al, 2020;Gaebler et al, 2021;Mor et al, 2021;Robbiani et al, 2020;Zhang et al, 2021) (Fig. 3F).…”

Section: Dramatic Difference In Maturation Of B Cell Responses Triggered By Sars-cov-2 Infection and Vaccinationmentioning

confidence: 96%

mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

Ivanova

Devlin

Buus

et al. 2021

Preprint

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Both SARS-CoV-2 infection and vaccination elicit potent immune responses. A number of studies have described immune responses to SARS-CoV-2 infection. However, beyond antibody production, immune responses to COVID-19 vaccines remain largely uncharacterized. Here, we performed multimodal single-cell sequencing on peripheral blood of patients with acute COVID-19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by this vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of the B and T cell antigen receptor rearrangement of individual lymphocytes, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. While both infection and vaccination induced robust innate and adaptive immune responses, our analysis revealed significant qualitative differences between the two types of immune challenges. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the observed dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes in patients but not in immunized subjects. Analysis of B and T cell receptor repertoires revealed that while the majority of clonal B and T cells in COVID-19 patients were effector cells, in vaccine recipients clonally expanded cells were primarily circulating memory cells. Importantly, the divergence in immune subsets engaged, the transcriptional differences in key immune populations, and the differences in maturation of adaptive immune cells revealed by our analysis have far-ranging implications for immunity to this novel pathogen.

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Section: Dramatic Difference In Maturation Of B Cell Responses Triggered By Sars-cov-2 Infection and Vaccinationmentioning

confidence: 96%

mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

Ivanova

Devlin

Buus

et al. 2021

Preprint

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“…These nAbs, including COVA1-18, COVA2-15, CV07-209, CC6.29, CC6.30, CC12.1, P008_108, 1212C2, and V H -Fc ab8, have been found to neutralize pseudovirus and/or live SARS-CoV-2 infection with high potency (IC 50 ≤ 40 ng/ml) [ 43 , 53 , 64 , 67 , 68 , 73 ]. The TAU-1145, TAU-2189, TAU-2230, and TAU-2303 nAbs, which recognize a key residue (G466) in the RBD, have been shown to neutralize both pseudotyped and live SARS-CoV-2 infection, inhibiting cell death or syncytium formation [ 45 ]. It has been noted that some RBD-targeting nAbs also neutralize infection by mutant variants of SARS-CoV-2 but at different potencies.…”

Section: Antigenic View Of the Ntd And Rbd Of Sars-cov-2 S Protein And Nab Binding Sitesmentioning

confidence: 99%

“…In vitro, a cocktail of CoV2-06 and CoV2-14 has been found to effectively prevent SARS-CoV-2 infection by escape mutants, but neither nAb had this effect individually [ 51 ]. The combination of TAU-2212 (which recognizes an unknown conformational epitope on the S protein) with an ACE2-competing, RBD-binding nAb (such as TAU-2230, TAU-2189, TAU-1145, or TAU-2303), and a non-ACE2-competing/RBD-targeting nAb (TAU-1099) has been shown to improve its efficiency in inhibiting SARS-CoV-2 infection [ 45 ]. Furthermore, the RBD-targeting nAbs COV2-2196 and COV2-2130, which block RBD-ACE2 binding but recognize the nonoverlapping sites on the RBD of SARS-CoV-2, have been shown to synergistically neutralize SARS-CoV-2 infection with improved neutralizing activity compared with each of the two nAbs alone [ 75 ].…”

Section: Antigenic View Of the Ntd And Rbd Of Sars-cov-2 S Protein And Nab Binding Sitesmentioning

confidence: 99%

Neutralizing antibodies for the prevention and treatment of COVID-19

Yang

Zhang

2021

Cell Mol Immunol

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus–cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

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“…Range for Abs levels: 10-160 ng/mL and 10-200 ng/mL for ADA-Abs and IFX-Abs, respectively. 24 was performed as described 25 using RBD-serum mix incubated with ACE2 coated plates.…”

Section: Sars-cov-2mentioning

confidence: 99%

Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα

Edelman-Klapper

Zittan

Shitrit

et al. 2021

Preprint

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Background: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear. Aim: to assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC). Methods: Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly. Results: Overall 258 subjects: 185 IBD (67 treated with anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNFα treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-S levels. Infection rate (~2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2. Conclusions: In this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.

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Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors

Cited by 43 publications

References 46 publications

mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

Neutralizing antibodies for the prevention and treatment of COVID-19

Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα

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