Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate

Uraki, Ryuta; Ito, Mutsumi; Kiso, Maki; Yamayoshi, Seiya; Iwatsuki‐Horimoto, Kiyoko; Furusawa, Yuri; Sakai‐Tagawa, Yuko; Imai, Masaki; Koga, Michiko; Yamamoto, Shinya; Adachi, Eisuke; Saito, Makoto; Tsutsumi, Takeya; Otani, Amato; Kikuchi, Tetsuhiro; Yotsuyanagi, Hiroshi; Halfmann, Peter; Pekosz, Andrew; Kawaoka, Yoshihiro

doi:10.1016/s1473-3099(23)00070-1

Cited by 58 publications

(65 citation statements)

References 6 publications

(6 reference statements)

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“…The recent experimental studies examining the efficacy of COVID-19 vaccines and antibodies against XBB.1.5 subvariant disclosed that the neutralizing activity against XBB.1.5 was considerably lower than that against the ancestral strain and BA.2, while similar immune evasion potential was observed for XBB. 1 and XBB.1.5 [60,61]. These studies confirmed that the high transmissibility and rapid surge of XBB.1.5 variant may be primarily due to the strong ACE2 binding affinity which is comparable only to the BA.2.75 variant, while retaining immune evasion similar to XBB.1 variant yields the overall better fitness tradeoff and leads to the observe growth advantages.…”

mentioning

confidence: 70%

“…Subsequent functional studies confirmed that the growth advantage and the increased transmissibility of the XBB.1.5 lineage may be a consequence of the retained neutralization resistance and the improved ACE2 binding affinity [57] These findings were consistent with the original deep mutational scanning (DMS) of the RBD residues using B.1, BA.1 and BA.2 backgrounds showing that F486 substitutions generally reduce ACE2 binding affinity due to decreased hydrophobic contacts, but these changes are more detrimental for F486S as compared to a modest loss for F486P [58,59]. The recent experimental studies examining the efficacy of COVID-19 vaccines and antibodies against XBB.1.5 subvariant disclosed that the neutralizing activity against XBB.1.5 was considerably lower than that against the ancestral strain and BA.2, while similar immune evasion potential was observed for XBB.1 and XBB.1.5 [60,61]. These studies confirmed that the high transmissibility and rapid surge of XBB.1.5 variant may be primarily due to the strong ACE2 binding affinity which is comparable only to the BA.2.75 variant, while retaining immune evasion similar to XBB.1 variant yields the overall better fitness tradeoff and leads to the observe growth advantages.…”

Section: Introductionmentioning

confidence: 99%

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Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages : Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes

Verkhivker

Alshahrani

Gupta

2023

Preprint

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The evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, protein stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2 , BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and identified energetic hotspots that can mediate the predicted increased stability and the enhanced binding affinity of the BA.2.75 and XBB.1.5 complexes. The results suggested a mechanism driven by the stability hotspots and a spatially localized group of the Omicron binding affinity centers, while allowing for functionally beneficial neutral Omicron mutations in other binding interface positions. A network-based community model for the analysis of non-additive epistatic contributions in the Omicron complexes is proposed revealing the key role of the binding hotspots R498 and Y501 in mediating community-based epistatic couplings with other Omicron sites and allowing for compensatory dynamics and binding energetic changes. The results also showed that mutations in the convergent evolutionary hotspot F486 can modulate not only local interactions but also rewire the global network of local communities in this region allowing the F486P mutation to restore both the stability and binding affinity of the XBB.1.5 variant which may explain the growth advantages over the XBB.1 variant. The results of this study are consistent with a broad range of functional studies rationalizing functional roles of the Omicron mutation sites that form a coordinated network of hotspots enabling balance of multiple fitness tradeoffs and shaping up a complex functional landscape of virus transmissibility.

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confidence: 70%

Section: Introductionmentioning

confidence: 99%

Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages : Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes

Verkhivker

Alshahrani

Gupta

2023

Preprint

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“…At the observed fold-change, plasma drug levels were anticipated to exceed those required for neutralization for at least 4 weeks after infusion. However, the currently predominant variants—for example, BQ.1, BQ.1.1, and XBB—have markedly reduced susceptibility to amubarvimab and romlusevimab ( 24 , 25 ). It remains unknown whether future variants will be susceptible to any of the previously proven efficacious monoclonal antibody products, including amubarvimab plus romlusevimab.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19

et al. 2023

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“…Besides, XBB.1.5 is also profoundly immunotolerant to humoral immunity induced by coronavirus disease 2019 (COVID‐19) vaccines (both monovalent and bivalent), commercial monoclonal antibodies, and convalescent plasma treatment. 13 , 15 , 16 , 17 It is the most resistant SARS‐CoV‐2 variant ever. Considering the high transmissibility and remarkable immune evasion, XBB.1.5 would probably become the cause of the next global wave.…”

Section: Introductionmentioning

confidence: 99%

A recombinant spike‐XBB.1.5 protein vaccine induces broad‐spectrum immune responses against XBB.1.5‐included Omicron variants of SARS‐CoV‐2

Alu

Hong

et al. 2023

MedComm

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The XBB.1.5 subvariant has drawn great attention owing to its exceptionality in immune evasion and transmissibility. Therefore, it is essential to develop a universally protective coronavirus disease 2019 vaccine against various strains of Omicron, especially XBB.1.5. In this study, we evaluated and compared the immune responses induced by six different spike protein vaccines targeting the ancestral or various Omicron strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. We found that spike-wild-type immunization induced high titers of neutralizing antibodies (NAbs) against ancestral SARS-CoV-2. However, its activity in neutralizing Omicron subvariants decreased sharply as the number of mutations in receptor-binding domain (RBD) of these viruses increased. Spike-BA.5, spike-BF.7, and spike-BQ.1.1 vaccines induced strong NAbs against BA.5, BF.7, BQ.1, and BQ.1.1 viruses but were poor in protecting against XBB and XBB.1.5, which have more RBD mutations. In sharp contrast, spike-XBB.1.5 vaccination can activate strong and broadly protective immune responses against XBB.1.5 and other common subvariants of Omicron. By performing correlation analysis, we found that the NAbs titers were negatively correlated with the number of RBD mutations in the Omicron subvariants. Vaccines with more RBD mutations can effectively overcome the immune resistance caused by the accumulation of RBD mutations, making spike-XBB.1.5 the most promising vaccine candidate against universal Omicron variants.

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Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate

Cited by 58 publications

References 6 publications

Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages : Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes

Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages : Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes

Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19

A recombinant spike‐XBB.1.5 protein vaccine induces broad‐spectrum immune responses against XBB.1.5‐included Omicron variants of SARS‐CoV‐2

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