Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Ragonnet‐Cronin, Manon; Nutalai, Rungtiwa; Huo, Jiandong; Dijokaite-Guraliuc, Aiste; Das, Raksha; Tuekprakhon, Aekkachai; Supasa, Piyada; Liu, Chang; Selvaraj, Muneeswaran; Groves, Natalie; Hartman, Hassan; Ellaby, Nicholas; Sutton, J. Mark; Bahar, Mohammad W.; Zhou, Daming; Fry, Elizabeth E.; Ren, Jingshan; Brown, Colin S; Klenerman, Paul; Dunachie, Susanna; Mongkolsapaya, Juthathip; Hopkins, Susan; Chand, Meera; Stuart, David I.; Screaton, Gavin; Rokadiya, Sakib

doi:10.1038/s41467-023-37826-w

Cited by 30 publications

(19 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BA.2.86 harbors numerous mutations that significantly deviate from the currently designated strains, with 33 spike mutations/14 receptor binding domain (RBD) mutations relative to BA.2 and 35 spike mutations/12 RBD mutations relative to XBB.1.5 (Figure 1A and 1C). Along with the shared mutations with XBB.1.5 (T19I, 24-26del, A27S, G142D, 144del, G339H, G446S, N460K, and F486P), additional mutations I332V, K356T, V445H, N450D, N481K, A484K and 483del on BA.2.86’s RBD are likely to enhance immune evasion as previously reported 2-6 . Many unusual mutations on the N-terminal domain (NTD), such as R21T, S50L, 69-70del, V127F, F157S, R158G, 211del, L212I, L216F, H245N, and A264D, may also alter the antigenicity of BA.2.86 7,8 .…”

Section: Mainsupporting

confidence: 68%

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86

Yang,

Yu,

Jian

et al. 2023

Preprint

View full text Add to dashboard Cite

The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86's NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86's transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86's infectivity.

show abstract

Section: Mainsupporting

confidence: 68%

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86

Yang,

Yu,

Jian

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Sotrovimab bound to all XBB-derived variants but not to BA.2.86.1. This is likely due to the presence of the K356T mutation in BA.2.86.1 RBD, that has been identified as conferring resistance to Sotrovimab 51 52 .…”

Section: Resultsmentioning

confidence: 99%

“…We further show that Sotrovimab, which retained partial antiviral activity against BQ.1.1 and XBB.1.5 (Bruel et al ., 2023), poorly acts on EG.5.1.3 and no longer binds or inhibits BA.2.86. This novel lineage carries numerous mutations known to allow mAb evasion (Wang et al ., 2023a), including the K356T substitution conferring resistance to Sotrovimab (Addetia et al ., 2023) (Ragonnet-Cronin et al ., 2023). Novel mAbs are under pre-clinical and clinical development (Cao et al ., 2022a; Moriyama et al, 2023; Park et al, 2022a).…”

Section: Discussionmentioning

confidence: 99%

“…Sotrovimab, which retained partial antiviral activity against BQ.1.1 and XBB.1.5 50 , poorly acted on EG.5.1.3 and no longer binds or inhibits BA.2.86.1 and JN.1. This novel lineage carries numerous mutations known to allow mAb evasion 28 , including the K356T substitution conferring resistance to Sotrovimab 51 52 . Novel mAbs are under pre-clinical and clinical development 11,60,61 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

Planas,

Staropoli,

Michel

et al. 2023

Preprint

View full text Add to dashboard Cite

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in November 2023. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.

show abstract

“…The COVID-19 pandemic illustrated the widespread consequences of viral spread. Mutant viruses can demonstrate many surface differences, which can reduce the neutralizing effects of antibodies and therapeutic agents and complicate diagnosis and detection . However, since a host receptor is an essential viral element needed for entry into the host cell, binding to the host receptor is maintained even when mutations occur.…”

Section: Discussionmentioning

confidence: 99%

A Host Receptor Nanodisc-Based Biosensor Platform for the Detection of a Specific Virus and Its Variants

Yoo,

Park,

Jwa

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

The host receptor is a key element in the initial stage of the virus entry into the host. The use of this host receptor is valuable as a sensing element for selectively and sensitively detecting specific viruses. Also, viruses tend to escape neutralizing antibodies through viral mutation but still utilize the cell entry process using the same host receptors, so it would be a powerful detection tool even for the mutant viruses. The angiotensinconverting enzyme 2 (ACE2) receptor, which is the representative host receptor, performs an essential function in facilitating viral penetration by interacting with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. In this study, we introduce a novel approach, where we fabricated a carbon nanotube field-effect transistor (CNT-FET) sensor and combined it with ACE2 receptor-embedded nanodisc (ND). ACE2 was produced using an E. coli expression system, purified, and integrated into the ND platform. ACE2 NDs showed robust functionality through interactions with a pseudotyped virus (PV) containing the spike protein, enabling sensitive detection of both SARS-CoV-2 and its genetic variations at 10 2 PFU/mL. The ACE ND-based sensor exhibited excellent selectivity by accurately differentiating SARS-CoV-2 wild-type and variants (Omicron, Delta) from other viruses (ZIKA and MERS-CoV). As a result of comparative analysis, ACE2 ND showed approximately 49% superior long-term functionality up to the second week compared to that of soluble ACE2. These findings highlight the high selectivity and sensitivity of host receptor-based sensors for detecting viral variants and provide a promising tool to prevent the spread of unknown viruses.

show abstract

Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy

Cited by 30 publications

References 40 publications

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86

Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

A Host Receptor Nanodisc-Based Biosensor Platform for the Detection of a Specific Virus and Its Variants

Contact Info

Product

Resources

About