Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation

Wang, Qian; Li, Zhiteng; Ho, Jerren; Guo, Yicheng; Yeh, Andre Yanchen; Mohri, Hiroshi; Liu, Mengmeng; Wang, Maple; Yu, Jian; Shah, Jainil P.; Chang, Joseph; Herbas, Favio; Yin, Michael T.; Sobieszczyk, Magdalena E.; Sheng, Zizhang; Liu, Lihong; Ho, David D.

doi:10.1016/s1473-3099(22)00694-6

Cited by 71 publications

(77 citation statements)

References 3 publications

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“…Sequences of the variants after one passage on IGROV-1 cells identified BA.4.6 and BQ.1.1 (Pango lineage B.1.1.529.4.6 and B.1.1.529.5.3.1.1.1.1.1.1, respectively according to Nextstrain, GISAID accession ID: BA.4.6: EPI_ISL_15729633 and BQ.1.1: EPI_ISL_15731523), indicating that no adaptative mutations were generated during this short culture period. As expected, BA.4.6 included R346T and N658S mutations 20 21 and BQ.1.1 carried R346T, K444T and N460K substitutions 22 . The spike mutations in the main Omicron subvariants are depicted Fig.…”

Section: Resultssupporting

confidence: 78%

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Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

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Section: Resultssupporting

confidence: 78%

“…For instance, BA.2.75.2, derived from BA.2, was first noted in India and Singapore and comprises R346T, F486S and D1199N substitutions 17-19 . BA.4.6 was detected in various countries, including USA and UK, and carries R346T and N658S mutations 20 21 . As of November 2022, BQ.1.1 became the main circulating lineage in many countries.…”

Section: Introductionmentioning

confidence: 99%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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“…Several aforementioned point mutants (R346T, N460K, and F486S) had been observed in prior SARS-CoV-2 variants, and their impact on mAb binding have been reported (Wang et al, 2022d; Wang et al, 2022e; Wang et al, 2022f). We therefore conducted structural modeling to understand the impact of the newly identified point mutants (Q183E, K444T, V445P, and F490S) on the binding of select mAbs ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…Perhaps the most important outcome of these mAb studies is the clinical implication for the use of mAbs to treat or prevent COVID-19. Previous SARS-CoV-2 variants have already successively knocked out the use of clinically authorized therapeutic antibodies (bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab), with bebtelovimab remaining as the only active monoclonal antibody against circulating SARS-CoV-2 strains (Iketani et al, 2022; Liu et al, 2022b; Wang et al, 2021; Wang et al, 2022d; Wang et al, 2022e; Wang et al, 2022f). Unfortunately, both BQ and XBB sublineages are now completely resistant to bebtelovimab, leaving us with no authorized antibody for treatment use.…”

Section: Discussionmentioning

confidence: 99%

“…The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to rage due to emergence of the Omicron variant and its descendant subvariants (Iketani et al, 2022; Liu et al, 2022b; Wang et al, 2022d; Wang et al, 2022e; Wang et al, 2022f). While the BA.5 subvariant is globally dominant at this time ( Figure 1A ), a diverse array of Omicron sublineages have arisen and are competing in the so-called “variant soup” (Callaway, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Wang

Iketani

et al. 2022

Preprint

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The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.

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Analyzing the emerging patterns of SARS‐CoV‐2 Omicron subvariants for the development of next‐gen vaccine: An observational study

Mohapatra,

Mishra,

Kandi

et al. 2023

Health Science Reports

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Background and AimUnderstanding the prevalence and impact of SARS‐CoV‐2 variants has assumed paramount importance. This study statistically analyzed to effectively track the emergence and spread of the variants and highlights the importance of such investigations in developing potential next‐gen vaccine to combat the continuously emerging Omicron subvariants.MethodsTransmission fitness advantage and effective reproductive number (Re) of epidemiologically relevant SARS‐CoV‐2 sublineages through time during the study period based on the GISAID data were estimated.ResultsThe analyses covered the period from January to June 2023 around an array of sequenced samples. The dominance of the XBB variant strain, accounting for approximately 57.63% of the cases, was identified during the timeframe. XBB.1.5 exhibited 37.95% prevalence rate from March to June 2023. Multiple variants showed considerable global influence throughout the study, as sporadically documented. Notably, the XBB variant demonstrated an estimated relative 28% weekly growth advantage compared with others. Numerous variants were resistant to the over‐the‐counter vaccines and breakthrough infections were reported. Similarly, the efficacy of mAB‐based therapy appeared limited. However, it's important to underscore the perceived benefits of these preventive and therapeutic measures were restricted to specific variants.ConclusionGiven the observed trends, a comprehensive next‐gen vaccine coupled with an advanced vaccination strategy could be a potential panacea in the fight against the pandemic. The findings suggest that targeted vaccine development could be an effective strategy to prevent infections. The study also highlights the need of global collaborations to rapidly develop and distribute the vaccines to ensure global human health.

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Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation

Cited by 71 publications

References 3 publications

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Analyzing the emerging patterns of SARS‐CoV‐2 Omicron subvariants for the development of next‐gen vaccine: An observational study

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