Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients DOI Creative Commons
Matthias Becker, Anne Cossmann,

Karsten Lürken

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Haemodialysis patients respond poorly to vaccination and continue be at-risk for severe COVID-19. Therefore, dialysis were among the first which a fourth COVID-19 was recommended. However, targeted information on how best maintain immune protection after SARS-CoV-2 vaccinations in groups remains limited. We provide, of our knowledge, time longitudinal response data controls triple BNT162b2 latter subsequent full-dose mRNA-1273. analysed systemic mucosal humoral IgG responses against receptor-binding domain (RBD) ACE2-binding inhibition towards variants concern including Omicron Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell by interferon γ release assay. After vaccination, anti-RBD B.1 ACE2 binding reached peak levels patients, but remained inferior compared controls. Whilst detected B.1-specific 84% three doses, variant only detectable 38% samples declining 16% before vaccination. By using mRNA-1273 as dose, immunity all tested strongly augmented 80% having Omicron-specific inhibition. Modest declines second restored third dose significantly increased Our support current advice four-dose immunisation scheme individuals such haemodialysis patients. conclude that administration part mixed mRNA boost prevent could also beneficial other impaired individuals. Additionally, strategic application vaccine regimens may an immediate evasion potential.

Language: Английский

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies DOI Creative Commons
Tetsuya Inoue, Yuichiro Yamamoto,

Kaoru Sato

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109363 - 109363

Published: Feb. 29, 2024

Highlights•Anti-SARS-CoV-2 bispecific Abs can be generated by combining non-neutralizing Abs•Anti-S2 antibody CvMab-62 recognizes a novel epitope upstream of S2 stem helix•Bispecific antibodies inhibit spike-mediated membrane fusogenic mechanism•Bispecific restore antiviral activity against bebtelovimab-resistant BQ.1.1SummaryA current challenge is the emergence SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that evade immune defenses, thereby limiting drug effectiveness. Emergency-use drugs, including widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue which combine targeting abilities two with distinct epitopes. We engineered neutralizing in IgG-scFv format from initially antibodies, CvMab-6 (which binds receptor-binding domain [RBD]) (targeting spike protein subunit adjacent known anti-S2 epitope). Furthermore, we created incorporating scFv bebtelovimab our antibody, demonstrating significant restoration effectiveness variants. This study highlights existing less anti-RBD revive therapeutics compromised immune-evading variants.Graphical abstract

Language: Английский

Citations

5
Revolutionizing SARS-CoV-2 omicron variant detection: Towards faster and more reliable methods DOI
Dan Li, Cai Sun,

Pengfei Zhuang

et al.

Talanta, Journal Year: 2023, Volume and Issue: 266, P. 124937 - 124937

Published: July 12, 2023

Language: Английский

Citations

11
A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation DOI Creative Commons
Saskia C. Stein, Guido Hansen, George Ssebyatika

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

ABSTRACT The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by emergence variants concern (VOCs), which have acquired mutations to escape neutralizing (nAbs). These are not evenly distributed on RBD surface but cluster several distinct surfaces, suggesting an influence targeted epitope capacity neutralize a broad range VOCs. Here, we identified potent nAb from convalescent patients Except for Lambda and BA.2.86 variants, this efficiently inhibited entry most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, EG.5.1 limited extent also BA.4/5, BA.4.6, BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced viral load in lung infected hamsters, prevented severe pathology typical infections. An X-ray structure nAb-RBD complex revealed that does fall into any conventional classes provided insights its neutralization properties. Our findings highlight conserved within should be preferably inform rational vaccine development. IMPORTANCE Therapeutic effective preventing disease infection constitute important option pandemic preparedness, virus (e.g., mutation L452) confer resistance many such antibodies. identify human antibody elevated barrier characterize interaction functionally structurally at atomic level. A direct comparison reported same illustrates differences interface, providing breadth binding. relevance extended profiling combination biochemical structural characterization antibody-RBD selection future antibodies, may accelerate control potential pandemics.

Language: Английский

Citations

4
Longitudinal analysis of immune responses to SARS-CoV-2 recombinant vaccine S-268019-b in phase 1/2 prime-boost study DOI Creative Commons

Masaya Fujitani,

Xiuyuan Lu, Ryo Shinnakasu

et al.

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

Published: March 5, 2025

The durability of vaccine-induced immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for preventing infection, especially disease. This follow-up report from a phase 1/2 study S-268019-b (a recombinant spike protein vaccine) after homologous booster vaccination confirms its long-term safety, tolerability, and immunogenicity. Booster with resulted in an enhancement serum neutralizing antibody (NAb) titers broad range viral neutralization. Single-cell profiling revealed persistent mature antigen-specific B cells T follicular helper cells, increased B-cell receptor diversity. expansion B- T-cell repertoires presence cross-reactive NAbs targeting conserved epitopes within the receptor-binding domain following accounted broad-spectrum activity. These findings highlight potential provide robust protection against SARS-CoV-2 variants, addressing critical challenge ongoing fight disease 2019 (COVID-19).

Language: Английский

Citations

0
Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients DOI Creative Commons
Matthias Becker, Anne Cossmann,

Karsten Lürken

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Haemodialysis patients respond poorly to vaccination and continue be at-risk for severe COVID-19. Therefore, dialysis were among the first which a fourth COVID-19 was recommended. However, targeted information on how best maintain immune protection after SARS-CoV-2 vaccinations in groups remains limited. We provide, of our knowledge, time longitudinal response data controls triple BNT162b2 latter subsequent full-dose mRNA-1273. analysed systemic mucosal humoral IgG responses against receptor-binding domain (RBD) ACE2-binding inhibition towards variants concern including Omicron Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell by interferon γ release assay. After vaccination, anti-RBD B.1 ACE2 binding reached peak levels patients, but remained inferior compared controls. Whilst detected B.1-specific 84% three doses, variant only detectable 38% samples declining 16% before vaccination. By using mRNA-1273 as dose, immunity all tested strongly augmented 80% having Omicron-specific inhibition. Modest declines second restored third dose significantly increased Our support current advice four-dose immunisation scheme individuals such haemodialysis patients. conclude that administration part mixed mRNA boost prevent could also beneficial other impaired individuals. Additionally, strategic application vaccine regimens may an immediate evasion potential.

Language: Английский

Citations

17