Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19

Pathogens, Journal Year: 2024, Volume and Issue: 13(12), P. 1109 - 1109

Published: Dec. 15, 2024

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing individuals infected with dengue virus are known to be associated severe disease upon reinfection different serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types ADE have been proposed: (1) Fc receptor-dependent infection cells expressing receptors, such as macrophages by anti-spike antibodies, (2) receptor-independent epithelial and (3) cytokine production anti-nucleocapsid antibodies. This review focuses on the induced examining its potential role COVID-19 during contribution post-acute sequelae COVID-19, i.e., prolonged symptoms lasting at least months after acute phase disease. We also discuss protective effects recently identified that neutralize Omicron variants.

Language: Английский

---

Induction of IGHV3-53 public antibodies with broadly neutralising activity against SARS-CoV-2 including Omicron subvariants in a Delta breakthrough infection case

EBioMedicine, Journal Year: 2024, Volume and Issue: 110, P. 105439 - 105439

Published: Nov. 1, 2024

Language: Английский

---

Protein language model pseudolikelihoods capture features of in vivo B cell selection and evolution

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract B cell selection and evolution play crucial roles in dictating successful immune responses. Recent advancements sequencing technologies deep-learning strategies have paved the way for generating exploiting an ever-growing wealth of antibody repertoire data. The self-supervised nature protein language models (PLMs) has demonstrated ability to learn complex representations sequences been leveraged a wide range applications including diagnostics, structural modeling, antigen-specificity predictions. PLM-derived likelihoods used improve affinities vitro, raising question whether PLMs can capture predict features vivo. Here, we explore how general antibody-specific PLM-generated sequence pseudolikelihoods (SPs) relate vivo such as expansion, isotype usage, somatic hypermutation (SHM) at single-cell resolution. Our results demonstrate that type PLM region input significantly affect generated SP. Contrary previous vitro reports, observe negative correlation between SPs binding affinity, whereas SHM, antigen specificity were strongly correlated with SPs. By constructing evolutionary lineage trees clones from human mouse repertoires, SHMs are routinely among most likely mutations suggested by mutating residues lower absolute than conserved residues. findings highlight potential further suggest their assist discovery engineering. Key points - In contrast work (Hie et al., 2024), pseudolikelihood (SP) affinity. This be explained inherent germline bias posed training data difference settings. also reveal considerable V-gene family, isotype, amount (SHM). Moreover, labeled antigen-binding SP is consistent reconstructing trajectories, detected predictable SHM using PLMs. We (CDR3 or full V(D)J) provided model, well used, influence resulting

Language: Английский

---

Longitudinal profiling of B cells primed by mRNA vaccine and recalled by Omicron variants uncovers antibodies broadly neutralizing sarbecoviruses

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Regarding to the impact of ancestral SARS-CoV-2 immune imprinting on antibody responses emerging variants, what extent memory B cells elicited by wild-type (WT) spike can develop neutralizing breadth and potency in recalls is a key question. Here, we longitudinally tracked recognizing WT two individuals mRNA vaccine, from convalescence breakthrough infection acute phase reinfection. Comprehensive characterization 632 monoclonal antibodies (mAbs) those reveals that mAbs cloned after reinfection have dramatically enhanced potency, including 11 potently neutralize all tested variants KP.3. Among mAbs, 5 are classified into public clonotypes encoded IGHV3-53 or IGHV3-66, whereas rest belong rare clonotype IGHV3-74. Notably, IGHV3-74 even SARS-CoV-1 with minimum IC50 0.055 μg/ml. Structural functional analysis further suggests target novel epitope receptor-binding domain, best mAb, termed KXD352, highly resilient variations this epitope. Overall, study demonstrates both primed prototype vaccine achieve extraordinary repeated Omicron infections.

Language: Английский

---