Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Bruel, Timothée; Hadjadj, Jérôme; Maes, Piet; Planas, Delphine; Sève, Aymeric; Staropoli, Isabelle; Guivel‐Benhassine, Florence; Porrot, Françoise; Bolland, William-Henry; Nguyen, Yann; Casadevall, Marion; Charre, Caroline; Péré, Hélène; Veyer, David; Prot, Matthieu; Baidaliuk, Artem; Cuypers, Lize; Planchais, Cyril; Mouquet, Hugo; Baele, Guy; Mouthon, Luc; Hocqueloux, Laurent; Simon‐Lorière, Etienne; André, Emmanuel; Terrier, Benjamin; Prazuck, Thiérry; Schwartz, Olivier

doi:10.1038/s41591-022-01792-5

Cited by 283 publications

(325 citation statements)

References 36 publications

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“…However, several monoclonal antibodies available in clinical practice have shown decreased sensitivity to Omicron BA.1 and BA.2 variants. 28 Thus, broad-spectrum anti-SARS-CoV-2 antibodies, especially with potent activities against Omicron variants are currently in urgent need. Strikingly, we reconfirmed the strong efficacy of our previously discovered antibody, JMB2002, against Omicron BA.2 in both binding assays and pseudovirus neutralization assay, with comparable inhibition potency to Omicron BA.1 strain.…”

Section: Discussionmentioning

confidence: 99%

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Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins

Cao³

et al. 2022

Preprint

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The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies reveal that the BA.2 spike trimer have 11-fold and 2-fold higher potency to human ACE2 than the spike trimer from the wildtype and Omicron BA.1 strains. The structure of the BA.2 spike timer reveals that all three receptor-binding domains (RBD) in the spike trimer are in open conformation, ready for high affinity binding to human ACE2, providing the basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to have efficient inhibition of Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to the mouse ACE2 with high potency. In contrast, the wildtype spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants from human-cat-mouse-human circle, which could have important implications in establishing an effective strategy in combating viral infection.

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Section: Discussionmentioning

confidence: 99%

“…However, several monoclonal antibodies available in clinical practice have shown decreased potency to Omicron BA.1 and BA.2 variants. 31 Thus, broad-spectrum anti-SARS-CoV-2 antibodies, especially with potent activities against Omicron variants are currently in urgent need.…”

Section: Discussionmentioning

confidence: 99%

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins

Cao³

et al. 2022

Preprint

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“…Our novel findings have immediate implications for vaccination and therapeutic strategies during the ongoing COVID-19 pandemic. The importance of our findings is emphasized by recent concerns regarding the limited efficacy of monoclonal antibodies against the omicron variant, 8 , 9 as passive antibody prophylaxis is being considered as an alternative strategy in efforts to protect transplant patients. Until new vaccines, or other strategies, offering better protection against VOCs become available, our data indicate that boosting vulnerable groups improves antibody responses (including neutralizing responses) and cellular immunity, may be an acceptable strategy.…”

mentioning

confidence: 81%

Fourth BNT162b2 vaccination neutralization of omicron infection after heart transplantation

Peled¹,

Afek²,

Nemet³

et al. 2022

The Journal of Heart and Lung Transplantation

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“…Owing to the continuous SARS-CoV-2 evolution caused by mutations and recombination, numerous genetically distinct SARS-CoV-2 lineages have emerged, and five major variants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and the newly identified micron (B.1.1.1.529 and BA), have been designed sequentially based on criteria such as various transmissibility and the ability to escape immunity [1][2][3][4][5][6]. Most mutations of SARS-CoV-2 concern variants primarily clustered on the NTD and RBD, two regions of spike S1, the two major domains being targeted by neutralizing antibodies [5,[7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Yuan

Chen

Zhu

et al. 2022

Preprint

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Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially the Omicron variant, have impaired the efficacy of existing vaccines and most therapeutic antibodies, highlighting the need for additional antibody-based tools that can efficiently neutralize emerging SARS-CoV-2 variants. The use of a “single” agent to simultaneously target multiple distinct epitopes on the spike is desirable to overcome the neutralizing escape of SARS-CoV-2 variants. Herein, we generated a human-derived IgG-like bispecific antibody (bsAb), Bi-Nab35B5-47D10, which successfully retained the specificity and simultaneously bound to the two distinct epitopes on RBD and S2. Bi-Nab35B5-47D10 showed improved spike binding breadth among wild-type (WT) SARS-CoV-2, variants of concern (VOCs) and variants being monitored (VBMs) compared with its parental mAbs. Furthermore, pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2), Omicron BA.1 and Omicron BA.2. Crucially, Bi-Nab35B5-47D10 substantially improved neutralizing activity against Omicron BA.1 (IC50= 27.3 ng/mL) and Omicron BA.2 (IC50= 121.1 ng/mL) compared with their parental mAbs. Therefore, Bi-Nab35B5-47D10 represents a potential effective countermeasure against SARS-CoV-2 Omicron and other variants of concern.ImportanceThe new highly contagious SARS-CoV-2 Omicron variant caused substantial breakthrough infections and has become the dominant strain in countries across the world. Omicron variants usually bear high mutations in the spike protein and exhibit considerable escape of most potent neutralization monoclonal antibodies and reduced efficacy of current COVID-19 vaccines. The development of neutralizing antibodies with potent efficacy against the Omicron variant is still an urgent priority. Here, we generated a bsAb, Bi-Nab35B5-47D10, that simultaneously targets SARS-CoV-2 RBD and S2 and improved neutralizing potency and breadth against SARS-CoV-2 WT and the tested variants compared with their parental antibodies. Notably, Bi-Nab35B5-47D10 has more potent neutralizing activity against the VOC Omicron pseudotyped virus. Therefore, Bi-Nab35B5-47D10 is a feasible and potentially effective strategy to treat and prevent COVID-19.

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Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

Cited by 283 publications

References 36 publications

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins

Fourth BNT162b2 vaccination neutralization of omicron infection after heart transplantation

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

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