Biparatopic antibodies: therapeutic applications and prospects DOI Creative Commons
David L. Niquille, Kyle M. Fitzgerald, Nimish Gera

et al.

mAbs, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 4, 2024

Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and bispecific (bsAbs) that can make bpAbs effective therapeutics for various indications, including oncology infectious diseases. lead to superior affinity specificity, promote antagonism, lock target conformation, result in higher-order clustering. Such antibody-target complexes elicit strong agonism, increase immune effector function, or rapid downregulation lysosomal trafficking. These are not only attractive properties therapeutic but increasingly being explored other modalities such as antibody-drug conjugates, T-cell engagers chimeric antigen receptors. Recent advances bpAb engineering have enabled the construction ever more sophisticated formats starting show promise clinic.

Language: Английский

Mechanisms of SARS-CoV-2 entry into cells DOI Creative Commons
Cody B. Jackson, Michael Farzan, Bing Chen

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 3 - 20

Published: Oct. 5, 2021

Language: Английский

Citations

2511
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma DOI Creative Commons
Constantinos Kurt Wibmer, Frances Ayres, Tandile Hermanus

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(4), P. 622 - 625

Published: March 2, 2021

Language: Английский

Citations

1235
Circular RNA vaccines against SARS-CoV-2 and emerging variants DOI Creative Commons
Liang Qu, Zongyi Yi, Yong Shen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1728 - 1744.e16

Published: April 1, 2022

As the emerging variants of SARS-CoV-2 continue to drive worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report circular RNA (circRNA) vaccine elicited potent neutralizing antibodies T cell responses by expressing trimeric RBD spike protein, providing robust protection against in both mice rhesus macaques. Notably, circRNA enabled higher durable antigen production than 1mΨ-modified mRNA proportion distinct Th1-skewed immune responses. Importantly, found circRNARBD-Omicron induced Omicron but not Delta variant. In contrast, circRNARBD-Delta protected or functioned as booster after two doses either native- Delta-specific vaccination, making it favorable choice current concern (VOCs) SARS-CoV-2.

Language: Английский

Citations

401
Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy DOI Creative Commons
Qianqian Zhang, Rong Xiang, Shanshan Huo

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 11, 2021

Abstract The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection has resulted in an unprecedented setback for global economy and health. SARS-CoV-2 exceptionally high level transmissibility extremely broad tissue tropism. However, the underlying molecular mechanism responsible sustaining this degree virulence remains largely unexplored. In article, we review current knowledge crucial information about how attaches on surface host cells through a variety receptors, such as ACE2, neuropilin-1, AXL, antibody–FcγR complexes. We further explain its spike (S) protein undergoes conformational transition from prefusion to postfusion with help proteases like furin, TMPRSS2, cathepsins. then ongoing experimental studies clinical trials antibodies, peptides, or small-molecule compounds anti-SARS-CoV-2 activity, discuss these antiviral therapies targeting host–pathogen interaction could potentially suppress viral attachment, reduce exposure fusion peptide curtail membrane block formation six-helix bundle (6-HB) core. Finally, specter rapidly emerging variants deserves serious broad-spectrum drugs vaccines long-term prevention control COVID-19 future.

Language: Английский

Citations

308
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma DOI Creative Commons
Constantinos Kurt Wibmer, Frances Ayres, Tandile Hermanus

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Jan. 19, 2021

Abstract SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains the spike protein. Here, we show that pseudovirus expressing protein completely escapes three classes therapeutically relevant antibodies. This also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight prospect reinfection with antigenically distinct variants and foreshadows reduced efficacy spike-based vaccines.

Language: Английский

Citations

284
Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants DOI Creative Commons
Jianliang Xu, Kai Xu, Seolkyoung Jung

et al.

Nature, Journal Year: 2021, Volume and Issue: 595(7866), P. 278 - 282

Published: June 7, 2021

Abstract Since the start of COVID-19 pandemic, SARS-CoV-2 has caused millions deaths worldwide. Although a number vaccines have been deployed, continual evolution receptor-binding domain (RBD) virus challenged their efficacy. In particular, emerging variants B.1.1.7, B.1.351 and P.1 (first detected in UK, South Africa Brazil, respectively) compromised efficacy sera from patients who recovered immunotherapies that received emergency use authorization 1–3 . One potential alternative to avert viral escape is camelid VHHs (variable heavy chain domains antibody (also known as nanobodies)), which can recognize epitopes are often inaccessible conventional antibodies 4 Here, we isolate anti-RBD nanobodies llamas mice engineered produce cloned alpacas, dromedaries Bactrian camels. We identified two groups highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region conserved coronaviruses but rarely targeted human antibodies. 2 almost exclusively focused RBD–ACE2 interface does not neutralize carry E484K or N501Y substitutions. However, group retain full neutralization activity against these when expressed homotrimers, and—to our knowledge—rival most potent produced date. These findings suggest multivalent overcome mutations through separate mechanisms: enhanced avidity for ACE2-binding recognition largely Therefore, although new mutants will continue emerge, represent promising tools prevent mortality compromised.

Language: Английский

Citations

206
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19 DOI Creative Commons
Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro

et al.

Immunity, Journal Year: 2021, Volume and Issue: 54(11), P. 2650 - 2669.e14

Published: Sept. 4, 2021

Language: Английский

Citations

194
SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8 + T cell responses DOI Creative Commons
Benedikt Agerer, Maximilian Koblischke, Venugopal Gudipati

et al.

Science Immunology, Journal Year: 2021, Volume and Issue: 6(57)

Published: March 4, 2021

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations MHC-I-restricted epitopes after deep sequencing of 747 isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding a cell-free vitro assay. Reduced mutant was associated with decreased proliferation, IFN-γ production cytotoxic activity cells isolated from HLA-matched patients. Single RNA ex vivo expanded, tetramer-sorted patients further revealed qualitative differences the transcriptional response peptides. Our findings highlight capacity subvert surveillance through point viral epitopes.

Language: Английский

Citations

167
Neutralising antibody escape of SARS‐CoV‐2 spike protein: Risk assessment for antibody‐based Covid‐19 therapeutics and vaccines DOI Open Access
Daniele Focosi, Fabrizio Maggi

Reviews in Medical Virology, Journal Year: 2021, Volume and Issue: 31(6)

Published: March 16, 2021

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in could affect efficacy those treatments. Hence, monitoring mutations necessary to forecast readapt inventory therapeutics. Different phylogenetic nomenclatures have been used for currently circulating SARS-CoV-2 clades. has different hotspots mutation deletion, most dangerous immune escape being ones within receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, N501Y. Convergent evolution led combinations among In this review we focus on main variants concern, that is, so-called UK (B.1.1.7), South African (B.1.351) Brazilian (P.1) strains.

Language: Английский

Citations

162
Antibodies and Vaccines Target RBD of SARS-CoV-2 DOI Creative Commons

Long Min,

Qiu Sun

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: April 22, 2021

The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat global public health. On March 11, 2020, WHO had officially announced COVID-19 as pandemic. Therefore, it is vital find effective and safe neutralizing antibodies vaccines for COVID-19. critical domain (CND) that contained in receptor-binding (RBD) of spike protein (S protein) could lead highly potent antibody response well cross-protection other strains SARS. By using RBD an antigen, many are isolated essential therapeutics Furthermore, subunit vaccine, based on RBD, expected be safer than others, thus S more important target vaccine development. In this review, we focus targeting under current

Language: Английский

Citations

156