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

Xixian Chen,

Ling Li,

Ruiping Du

et al.

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

Repeated Omicron exposures redirect SARS-CoV-2–specific memory B cell evolution toward the latest variants DOI
Ryutaro Kotaki, Saya Moriyama,

Shintaro Oishi

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(761)

Published: Aug. 21, 2024

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses Omicron-based booster vaccines. Here, we analyzed specificity and neutralization activity memory B (B mem ) cells after repeated BA.5 exposure in individuals previously imprinted strain–based mRNA After a second exposure, with spike protein–skewed reactivity were promptly elicited, correlating preexisting antibody titers. Clonal lineage analysis identified BA.5-skewed that had redirected their from strain through somatic hypermutations. Moreover, exhibited accelerated development compared de novo derived naïve repertoires. This demonstrated greater resilience viral point mutation adaptation recent Omicron variants HK.3 JN.1, months suggesting existing elicited older vaccines can redirect toward newly evolving variants.

Language: Английский

Citations

5
Diversification of the VH3‐53 immunoglobulin gene segment by somatic hypermutation results in neutralization of SARS‐CoV‐2 virus variants DOI Creative Commons
Matthias Bruhn,

Maureen Obara,

Md. Abdus Salam

et al.

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(7)

Published: April 9, 2024

COVID-19 induces re-circulating long-lived memory B cells (MBC) that, upon re-encounter with the pathogen, are induced to mount immunoglobulin responses. During convalescence, antibodies subjected affinity maturation, which enhances antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single-cell RNA sequencing analysis of spike-specific from SARS-CoV-2 convalescent subject. After vaccination, matured infection-induced MBC underwent recall differentiated into plasmablasts. Furthermore, transcriptomic profiles newly activated transiently shifted toward ones atypical CXCR3

Language: Английский

Citations

4
Antibody drugs targeting SARS-CoV-2: Time for a rethink? DOI Open Access

Likeng Liang,

Bo Wang, Qing Zhang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116900 - 116900

Published: June 10, 2024

Language: Английский

Citations

4
Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies DOI Creative Commons
Miao Wang, Congcong Liu, Qing Fan

et al.

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Several vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing an opportunity to characterize the antibody response. In this study, we investigated monoclonal responses elicited by wild-type SARS-CoV-2 vaccination compared those natural infection mRNA vaccination. The analysis showed that encoded biased germline genes were shared between vaccinated naturally infected individuals. Among 35 clonotypes identified, besides well-known IGHV3-53 IGHV1-58, identified a class of IGHV4-59 characterized rapid response neutralizing activity, 3 doses vaccine. Members lineage exhibited similar sensitivity SARS-CoV-2, whereas different activities variants, especially various Omicron subvariants, BA.1, BA.2, BA.2.12.1, BA.4/5, BA.2.75. Structural BA.1 spike complexed with VacBB-639 revealed IGHV4-59-lineage belonged Class 2/3 group. Using sequence alignment, site-mutation assays, functional verification, two substitutions, N60K HFR3 S56G HCDR2, contributing opposite neutralization changes these subvariants. These results demonstrate importance somatic hypermutation evolution prototypical antigen-elicited terms their breadth potency variants.

Language: Английский

Citations

0
Identification of Two Immunoglobulin Light Chain Types and Expression of Immunoglobulin Diversity in Chinese Giant Salamander (Andrias davidianus) DOI

X. Liu,

Xiuzhu Sun,

Huyang Bao

et al.

Developmental & Comparative Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 105358 - 105358

Published: March 1, 2025

Language: Английский

Citations

0
Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters DOI Creative Commons

J. Ahmed,

Samantha J. Krosta,

M. Reimer

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction During rollout of mRNA-based COVID-19 vaccines, several jurisdictions extended the interval between first and second doses to prioritize wider population access limited vaccine supply. This study evaluated effects an dose on development antibody cell-mediated responses following primary series a subsequent booster dose. Methods Blood samples were collected from mRNA recipients at baseline longitudinally after each Samples analyzed for SARS-CoV-2-specific titers, neutralizing antibodies memory T cell responses. Results An was associated with improved breadth against both ancestral early SARS-CoV-2 variants, but not Omicron variants. Dose had no impact antigen-specific responses, or helper phenotypes responding cells cytokine production. The immune outcomes longer evident third vaccine. Discussion resulted in short-term benefits humoral immunity these transient context exposures. However, addition public health immunological extending may have been sustained absence boosters. These findings underscore importance evaluating dosing intervals during future candidates.

Language: Английский

Citations

0
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 DOI Creative Commons
Roy A. Ehling, Mason Minot, Max D. Overath

et al.

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

Published: April 1, 2024

ABSTRACT The Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring Red Queen hypothesis of evolutionary biology. generates neutralizing antibodies targeting SARS-CoV-2 spike protein’s receptor binding domain (RBD), crucial for host cell invasion, while virus evolves to evade antibody recognition. Here, we establish synthetic coevolution combining high-throughput screening RBD variant libraries with protein mutagenesis, surface display, deep sequencing. Additionally, train language machine learning model that predicts escape variants. Synthetic reveals antagonistic compensatory mutational trajectories variants, enhancing understanding this conflict.

Language: Английский

Citations

3
Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection DOI Creative Commons
Xun Wang, M Zhang,

Kaifeng Wei

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 464 - 464

Published: April 26, 2024

The rapid mutation of SARS-CoV-2 has led to multiple rounds large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes humoral cellular immunity responses several subvariants after remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, IFN-γ secreting CD4+/CD8+ T cell variants, we observed that each component exhibited distinct kinetics. Either induces relatively high level binding neutralizing titers against Omicron at an early time point, which rapidly decreases over time. Most 6 months post-breakthrough completely lost their activities BQ.1.1, CH.1.1, BA.2.86, JN.1 XBB subvariants. Individuals with exhibit imprinting shifting recall pre-existing BA.5/BF.7 neutralization antibodies. BA.5 group, frequency XBB.1.16-RBD specific cells, resting intermediate cells gradually increased On other hand, induced by WT/BA.5/XBB.1.16 spike trimer remains stable Overall, research indicates have declining levels but can provide some degree protection future exposure new antigens.

Language: Английский

Citations

3
Analysis of Immunoglobulin Organization and Complexity in Mink (Neovison vison) DOI
Xiaohua Yi,

Yanbo Qiu,

Shu-Hui Wang

et al.

Developmental & Comparative Immunology, Journal Year: 2024, Volume and Issue: 160, P. 105234 - 105234

Published: July 26, 2024

Language: Английский

Citations

3
Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19 DOI Creative Commons

Emi E. Nakayama,

Tatsuo Shioda

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

Citations

2