The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Lu, Lu; Chu, Allen Wing-Ho; Zhang, Ricky Ruiqi; Chan, Wan-Mui; Ip, Jonathan Daniel; Tsoi, Hoi-Wah; Chen, Lin-Lei; Cai, Jian‐Piao; Lung, David Christopher; Tam, Anthony Raymond; Yau, Yat-Sun; Kwan, Mike Yat Wah; To, Wing‐Kin; Tsang, Owen Tak‐Yin; Lee, Larry Lap-Yip; Yi, Haisu; Ip, Tak-Chuen; Poon, Rosana W.S.; Siu, Gilman Kit-Hang; Mok, Bobo Wing-Yee; Cheng, Vincent Chi-Chung; Chan, Kwok Hung; Yuen, Kwok‐Yung; Hung, Ivan; To, Kelvin Kai‐Wang

doi:10.1016/j.ebiom.2021.103544

Cited by 41 publications

(33 citation statements)

References 40 publications

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“…Studies have shown that there are many hydrophobic amino acids on the site of antigen and antibody binding ( 12 ), so we also took the sites that are mutated into hydrophobic amino acids in the S protein as the research objects of interest. We hypothesized that epitopes generated based on these mutated sites as well as the mutated sites in the most immunogenic region of the S protein named RBD ( 13 ) might be more likely to be presented to the cell surface by MHC molecules and recognized by T cells. In addition, the high-frequency D614G mutation that appeared in these five variants was also considered to be interesting, since several studies emphasized the impact of D614G variant on transmission effectiveness ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

Computer-Based Immunoinformatic Analysis to Predict Candidate T-Cell Epitopes for SARS-CoV-2 Vaccine Design

Mei

Gu²,

Shen³

et al. 2022

Front. Immunol.

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Since the first outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, its high infectivity led to its prevalence around the world in an exceptionally short time. Efforts have been made to control the ongoing outbreak, and among them, vaccine developments are going on high priority. New clinical trials add to growing evidence that vaccines from many countries were highly effective at preventing SARS-CoV-2 virus infection. One of them is B cell-based vaccines, which were common during a pandemic. However, neutralizing antibody therapy becomes less effective when viruses mutate. In order to tackle the problem, we focused on T-cell immune mechanism. In this study, the mutated strains of the virus were selected globally from India (B.1.617.1 and B.1.617.2), United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (P.1), and the overlapping peptides were collected based on mutation sites of S-protein. After that, residue scanning was used to predict the affinity between overlapping peptide and HLA-A*11:01, the most frequent human leukocyte antigen (HLA) allele among the Chinese population. Then, the binding free energy was evaluated with molecular docking to further verify the affinity changes after the mutations happen in the virus genomes. The affinity test results of three epitopes on spike protein from experimental validation were consistent with our predicted results, thereby supporting the inclusion of the epitope 374FSTFKCYGL382 in future vaccine design and providing a useful reference route to improve vaccine development.

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Section: Methodsmentioning

confidence: 99%

Computer-Based Immunoinformatic Analysis to Predict Candidate T-Cell Epitopes for SARS-CoV-2 Vaccine Design

Mei

Gu²,

Shen³

et al. 2022

Front. Immunol.

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“…It is possible that N501Y may induce neutralization resistance in the serum from convalescent COVID-19 patients 49 or the N501Y mutant may alter the availability of epitopes that are targeted by the antibodies. Moreover, resistance could be enhanced with the combination of E484K/K417N mutations 50 - 52 . The results are consistent to our data using monoclonal and polyclonal antibodies and the serum from convalescent patients and vaccinees (Figure 4 and 5 ), suggesting that N501Y/E484K/K417N mutations improve the inhibition of S-ACE2 interactions.…”

Section: Discussionmentioning

confidence: 99%

Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination

Zhang¹,

Zheng²,

Wang³

et al. 2022

Theranostics

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Rationale: Mutations of SARS-CoV-2, which is responsible for coronavirus disease 2019 (COVID-19), could impede drug development and reduce the efficacy of COVID-19 vaccines. Here, we developed a multiplexed Spike-ACE2 Inhibitor Screening (mSAIS) assay that can measure the neutralizing effect of antibodies across numerous variants of the coronavirus's Spike (S) protein simultaneously. Methods: The SARS-CoV-2 spike variant protein microarrays were prepared by printing 72 S variants onto a chemically-modified glass slides. The neutralization potential of purified anti-S antibodies and serum from convalescent COVID-19 patients and vaccinees to S variants were assessed with the mSAIS assay. Results: We identified new S mutations that are sensitive and resistant to neutralization. Serum from both infected and vaccinated groups with a high titer of neutralizing antibodies (NAbs) displayed a broader capacity to neutralize S variants than serum with low titer NAbs. These data were validated using serum from a large vaccinated cohort (n = 104) with a tiled S peptide microarray. In addition, similar results were obtained using a SARS-CoV-2 pseudovirus neutralization assay specific for wild-type S and five prevalent S variants (D614G, B.1.1.7, B.1.351, P.1, B.1.617.2), thus demonstrating that high antibody diversity is associated with high NAb titers. Conclusions: Our results demonstrate the utility of the mSAIS platform in screening NAbs. Moreover, we show that heterogeneous antibody populations provide a more protective effect against S variants, which may help direct COVID-19 vaccine and drug development.

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“…Although further studies involving more clinical strains and serum samples, especially using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization as performed by Lu et al [15] , are essential to obtain a firm conclusion, this study assessed neutralizing antibody titers using authentic SARS-CoV-2 variants. A majority of the studies in the literature employ pseudo-virus-mediated systems [16] , [17] because of the difficulty in handling SARS-CoV-2 with regards to the regulations and infectivity.…”

Section: Discussionmentioning

confidence: 99%

The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals

Uwamino¹,

Yokoyama²,

Shimura³

et al. 2022

Vaccine

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The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 ± 2.40 and 102.67 ± 2.28, respectively), whereas a low titer was measured for the beta variant (18.03 ± 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340)

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The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Cited by 41 publications

References 40 publications

Computer-Based Immunoinformatic Analysis to Predict Candidate T-Cell Epitopes for SARS-CoV-2 Vaccine Design

Computer-Based Immunoinformatic Analysis to Predict Candidate T-Cell Epitopes for SARS-CoV-2 Vaccine Design

Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination

The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals

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