Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects

SUMMARYSARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency rather than the antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

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The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model

Blood ◽

10.1182/blood-2009-03-208587 ◽

2010 ◽

Vol 115 (16) ◽

pp. 3341-3345 ◽

Cited By ~ 56

Author(s):

Ke Cheng ◽

Paolo Sportoletti ◽

Keisuke Ito ◽

John G. Clohessy ◽

Julie Teruya-Feldstein ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Mouse Model ◽

Transgenic Mice ◽

Transgenic Mouse ◽

Myeloid Leukemia ◽

Gene Mutations ◽

Transgenic Mouse Model ◽

Acute Myeloid

Abstract Although NPM1 gene mutations leading to aberrant cytoplasmic expression of nucleophosmin (NPMc+) are the most frequent genetic lesions in acute myeloid leukemia, there is yet no experimental model demonstrating their oncogenicity in vivo. We report the generation and characterization of a transgenic mouse model expressing the most frequent human NPMc+ mutation driven by the myeloid-specific human MRP8 promoter (hMRP8-NPMc+). In parallel, we generated a similar wild-type NPM trans-genic model (hMRP8-NPM). Interestingly, hMRP8-NPMc+ transgenic mice developed myeloproliferation in bone marrow and spleen, whereas nontransgenic littermates and hMRP8-NPM transgenic mice remained disease free. These findings provide the first in vivo evidence indicating that NPMc+ confers a proliferative advantage in the myeloid lineage. No spontaneous acute myeloid leukemia was found in hMPR8-NPMc+ or hMRP8-NPM mice. This model will also aid in the development of therapeutic regimens that specifically target NPMc+.

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In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model

Amino Acids ◽

10.1007/s00726-010-0662-8 ◽

2010 ◽

Vol 39 (5) ◽

pp. 1571-1580 ◽

Cited By ~ 16

Author(s):

Garikoitz Azkona ◽

Ditsa Levannon ◽

Yoram Groner ◽

Mara Dierssen

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Double Transgenic Mouse ◽

In Vivo Effects

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An anti-SARS-CoV-2 non-neutralizing antibody with Fc-effector function defines a new NTD epitope and delays neuroinvasion and death in K18-hACE2 mice

10.1101/2021.09.08.459408 ◽

2021 ◽

Author(s):

Guillaume Beaudoin-Bussières ◽

Yaozong Chen ◽

Irfan Ullah ◽

Jérémie Prévost ◽

William D. Tolbert ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Animal Models ◽

Mouse Model ◽

Transgenic Mouse ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Transgenic Mouse Model ◽

Effector Function ◽

Effector Functions

SummaryEmerging evidence in animal models indicate that both neutralizing activity and Fc- mediated effector functions of neutralizing antibodies contribute to protection against SARS-CoV-2. It is unclear if antibody effector functions alone could protect against SARS-CoV-2. Here we isolated CV3-13, a non-neutralizing antibody from a convalescent individual with potent Fc-mediated effector functions that targeted the N- terminal domain (NTD) of SARS-CoV-2 Spike. The cryo-EM structure of CV3-13 in complex with SAR-CoV-2 spike revealed that the antibody bound from a distinct angle of approach to a novel NTD epitope that partially overlapped with a frequently mutated NTD supersite in SARS-CoV-2 variants. While CV3-13 did not alter the replication dynamics of SARS-CoV-2 in a K18-hACE2 transgenic mouse model, an Fc-enhanced CV3-13 significantly delayed neuroinvasion and death in prophylactic settings. Thus, we demonstrate that efficient Fc-mediated effector functions can contribute to the in vivo efficacy of anti-SARS-CoV-2 monoclonal antibodies in the absence of neutralization.

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