The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Liu, Chang; Zhou, Daming; Nutalai, Rungtiwa; Hme., Duyvesteyn; Tuekprakhon, Aekkachai; Ginn, H.; Dejnirattisai, Wanwisa; Supasa, Piyada; Mentzer, Alexander J.; Wang, Beibei; Case, James Brett; Zhao, Yuguang; Skelly, Donal; Chen, Rita E.; Johnson, Síle A.; Ritter, Thomas G.; Mason, Chris; Malik, Tariq; Temperton, Nigel; Paterson, Neil G.; Williams, Mark A.; Hall, David R.; Clare, Daniel K.; Howe, Andrew; Goulder, Philip; Fry, Elizabeth E.; Diamond, Michael S.; Mongkolsapaya, Juthathip; Ren, Jingshan; Stuart, D.I.; Screaton, Gavin

doi:10.1016/j.chom.2021.11.013

Cited by 58 publications

(107 citation statements)

References 50 publications

(78 reference statements)

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“…In addition to concordant epitope targeting, we also found consistent V gene usage in the antibody response to all three variants we investigated. Although some recent studies have noted enrichment for IGHV4-39 and closely related V H genes in Beta-infection ( 56, 57 ) we did not observe any differences in the usage of these genes. Our findings likely highlight the difference between the neutralizing antibody repertoires investigated in prior studies compared to the total binding repertoires examined here and emphasize the insights to be gleaned by taking a broader perspective.…”

Section: Discussioncontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Recent studies have shown that Y501-dependent mAbs derived from IGHV4-39 and related genes are overrepresented among neutralizing antibodies isolated from Beta-infected individuals ( 56, 57 ). Structural evidence suggests that bias toward these genes may in part be due to germline-encoded residues Y35 and Y54 in complementarity-determining region (CDR) H1 and H2, respectively ( 56 ). We therefore analyzed the observed frequency of germline genes encoding these residues (IGHV4-30, IGHV4-31, IGHV4-39, and IGHV4-61) among Beta- and Gamma-binding B cells but found no significant differences based on infecting variant (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Lima

Mukhamedova

Johnston

et al. 2022

Preprint

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While humoral immune responses to infection or vaccination with ancestral SARS-CoV-2 have been well-characterized, responses elicited by infection with variants are less understood. Here we characterized the repertoire, epitope specificity, and cross-reactivity of antibodies elicited by Beta and Gamma variant infection compared to ancestral virus. We developed a high-throughput approach to obtain single-cell immunoglobulin sequences and isolate monoclonal antibodies for functional assessment. Spike-, RBD- and NTD-specific antibodies elicited by Beta- or Gamma-infection exhibited a remarkably similar hierarchy of epitope immunodominance for RBD and convergent V gene usage when compared to ancestral virus infection. Additionally, similar public B cell clones were elicited regardless of infecting variant. These convergent responses may account for the broad cross-reactivity and continued efficacy of vaccines based on a single ancestral variant.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Lima

Mukhamedova

Johnston

et al. 2022

Preprint

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“…Several of these have been designated variants of concern (VoC) (https://www.cdc.gov/coronavirus/2019-ncov/variants/variantclassifications.html) and have led to successive waves of infection: first Alpha (Supasa et al, 2021), then Delta (Liu et al, 2021a), then Omicron (Dejnirattisai et al, 2022) spread globally becoming the dominant variants. Alongside these, Beta (Zhou et al, 2021) and Gamma (Dejnirattisai et al, 2021b) case-numbers/variants-distribution-of-case-data-29-april-2022#omicron) and, although the disease is less severe, particularly in the vaccinated, the scale of the outbreak has still led to a large number of deaths (Nealon and Cowling, 2022).…”

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confidence: 99%

“…Mutation of the ACE2 interacting surface may also give advantage by increased ACE2 affinity for S, or possibly altering receptor tropism (Zahradnik et al, 2021). Increased ACE2 affinity has been found in VoC compared to ancestral strains (Dejnirattisai et al, 2021b;Liu et al, 2021a;Supasa et al, 2021;Zhou et al, 2021), potentially conferring a transmission advantage, but affinity is not increased in Omicron BA.1 (Dejnirattisai et al, 2022) and only marginally in BA.2 (Nutalai et al, 2022).…”

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confidence: 99%

Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Tuekprakhon

Huo

Nutalai

et al. 2022

Preprint

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The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

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What makes SARS‐CoV‐2 unique? Focusing on the spike protein

Qian,

Zhang,

Wang

et al. 2024

Cell Biology International

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Severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) seriously threatens public health and safety. Genetic variants determine the expression of SARS‐CoV‐2 structural proteins, which are associated with enhanced transmissibility, enhanced virulence, and immune escape. Vaccination is encouraged as a public health intervention, and different types of vaccines are used worldwide. However, new variants continue to emerge, especially the Omicron complex, and the neutralizing antibody responses are diminished significantly. In this review, we outlined the uniqueness of SARS‐CoV‐2 from three perspectives. First, we described the detailed structure of the spike (S) protein, which is highly susceptible to mutations and contributes to the distinct infection cycle of the virus. Second, we systematically summarized the immunoglobulin G epitopes of SARS‐CoV‐2 and highlighted the central role of the nonconserved regions of the S protein in adaptive immune escape. Third, we provided an overview of the vaccines targeting the S protein and discussed the impact of the nonconserved regions on vaccine effectiveness. The characterization and identification of the structure and genomic organization of SARS‐CoV‐2 will help elucidate its mechanisms of viral mutation and infection and provide a basis for the selection of optimal treatments. The leaps in advancements regarding improved diagnosis, targeted vaccines and therapeutic remedies provide sound evidence showing that scientific understanding, research, and technology evolved at the pace of the pandemic.

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The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

Cited by 58 publications

References 50 publications

Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum

What makes SARS‐CoV‐2 unique? Focusing on the spike protein

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