Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2

Luo, Mengxiao; Zhou, Biao; Madan, Bharat; Tang, Bingjie; Chen, Bo‐Hao; Zhou, Runhong; Liu, Huan; Katsamba, Phinikoula S.; Au, Ka‐Kit; Man, Hiu-On; To, Kelvin Kai‐Wang; Yuen, Kwok‐Yung; Shapiro, Lawrence; Dang, Shangyu; Ho, David D.; Chen, Zhiwei

doi:10.1080/22221751.2022.2146538

Cited by 8 publications

(16 citation statements)

References 65 publications

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“…The antibody P2D9, identified in Luo et al 2023, was obtained from the memory B cells of individuals vaccinated with the BNT162b2-vaccine (31). These individuals also had breakthrough BA.1 infection (31). P2D9 was found to neutralize all tested variants of concern and omicron sublineages (31).…”

Section: Resultsmentioning

confidence: 99%

“…Our antibody array primarily consists of memory B-cell derived antibodies that are studied to be broadly neutralizing against different variants (23, 24, 30). Our results support the empirical results that our antibody array, primarily consisting of broadly neutralizing antibodies, maintains their efficacy across different variants (23, 24, 30). The presence of such broadly neutralizing antibodies also may indicate a level of prevalence of memory B-cells within vaccinated individuals that generate such antibodies (23, 30, 50, 51).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to this limitation, in our in silico method we use antibodies that have been studied to be produced upon memory B-cell stimulation and neutralize SARS-CoV-2 variants (23, 24, 30). Given a larger sample size of memory B-cell derived antibodies, we believe that this approach will be a more accurate and comprehensive approach to assess how well prior vaccination and/or infection will protect against infection and severe disease against future SARS-CoV-2 variants and other threats to public and personal health.…”

Section: Discussionmentioning

confidence: 99%

“…Five of the seven selected antibodies were derived from memory B-cells from human patients. (23, 24, 30). Antibodies are listed in Table 2.…”

Section: Methodsmentioning

confidence: 99%

“…We downloaded other available SARS-CoV-2 Spike RBD crystal structures from the Protein Data Bank (PDB) (28). We derived the WT and BA.1/B.1.1.529 RBD structures from the Protein Data Bank as they represent empirically derived structures from an RBD-Antibody or RBD-ACE2 complex (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). For every RBD-antibody and RBD-ACE2 complex we isolated on PDB, we extracted the RBD structure from that complex.…”

Section: Viral Proteinsmentioning

confidence: 99%

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Predicting Antibody and ACE2 Affinity for SARS-CoV-2 BA.2.86 and JN.1 withIn SilicoProtein Modeling and Docking

Yasa,

Guirales-Medrano,

Machado

et al. 2023

Preprint

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The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed “Pirola”) has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted anin silicoanalysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86’s high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples forin silicostudies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variant’s potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.

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Section: Resultsmentioning

confidence: 99%