Unlocking the potential of in silico approach in designing antibodies against SARS-CoV-2 DOI Creative Commons

Tasshitra R. Subramaniam,

Siti Aisyah Mualif, Weng Howe Chan

et al.

Frontiers in Bioinformatics, Journal Year: 2025, Volume and Issue: 5

Published: Feb. 13, 2025

Antibodies are naturally produced safeguarding proteins that the immune system generates to fight against invasive invaders. For centuries, they have been artificially and utilized eradicate various infectious diseases. Given ongoing threat posed by COVID-19 pandemics worldwide, antibodies become one of most promising treatments prevent infection save millions lives. Currently, in silico techniques provide an innovative approach for developing antibodies, which significantly impacts formulation antibodies. These develop with great specificity potency diseases such as SARS-CoV-2 using computational tools algorithms. Conventional methods designing frequently costly time-consuming. However, offers a contemporary, effective, economical paradigm creating next-generation especially accordance recent developments bioinformatics. By utilizing multiple antibody databases high-throughput approaches, unique construct can be designed , facilitating accurate, reliable, secure development human use. Compared their traditionally developed equivalents, large number -designed advanced swiftly clinical trials became accessible sooner. This article helps researchers more quickly affordably giving them access current information on approaches creation.

Language: Английский

SARS-CoV-2 evolution in the Omicron era DOI
Cornelius Roemer, Daniel J. Sheward, Ryan Hisner

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(11), P. 1952 - 1959

Published: Oct. 16, 2023

Language: Английский

Citations

83
Implications of diversity in sperm size and function for sperm competition and fertility DOI Open Access

Montserrat Gomendio,

Eduardo R. S. Roldán

The International Journal of Developmental Biology, Journal Year: 2008, Volume and Issue: 52(5-6), P. 439 - 447

Published: Jan. 1, 2008

Sperm competition is now recognised as a potent selective force shaping many male reproductive traits. While the influence of sperm on number widely accepted, its effects upon size remain controversial. It had been traditionally assumed that there trade-off between and size, so an increase in would result decrease under conditions competition. Contrary to this prediction, we proposed some time ago favours because longer swim faster are more likely win race fertilize ova. Comparative studies species show taxa such relationship exists, but consequences may vary depending environment which spermatozoa have compete. We present new evidence showing mammals at higher speeds. also mean swimming speed highly correlated with maximum speed, even if fastest fertilize, both measures informative. When individuals same compared, ratios dimensions different components, well shape head, seem better explaining velocity. Finally, determine fertility. Other shown competitive contexts, males fertilization success. conclude available supports our original hypothesis.

Language: Английский

Citations

182
The evolutionary and functional significance of germline immunoglobulin gene variation DOI Creative Commons

Matt Pennell,

Oscar L. Rodriguez, Corey T. Watson

et al.

Trends in Immunology, Journal Year: 2022, Volume and Issue: 44(1), P. 7 - 21

Published: Dec. 2, 2022

The recombination between immunoglobulin (IG) gene segments determines an individual's naïve antibody repertoire and, consequently, (auto)antigen recognition. Emerging evidence suggests that mammalian IG germline variation impacts humoral immune responses associated with vaccination, infection, and autoimmunity – from the molecular level of epitope specificity, up to profound changes in architecture repertoires. These links variants immunophenotype raise question on evolutionary causes consequences diversity within loci. We discuss why extreme loci remains a mystery, resolving this is important for design more effective vaccines therapeutics, how recent multiple lines inquiry may help us do so.

Language: Английский

Citations

41
Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2 DOI Creative Commons
Kuan-Ying A. Huang, Xiaorui Chen, Arpita Mohapatra

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 19, 2023

Abstract Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination showed that they recognize an immunogenic patch on the internal surface core RBD, which faces inwards is hidden “down” state. These broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta Delta variants some are effective other sarbecoviruses. observed continuum partially overlapping antibody epitopes from lower to upper part inner face RBD extend towards receptor-binding motif. The majority substantially compromised by three mutational hotspots (S371L/F, S373P S375F) Omicron BA.1, BA.2 BA.4/5 RBD. By contrast, IY-2A induces partial unfolding this variable region interacts with conserved conformational epitope tolerate all antigenic variations diverse sarbecoviruses as well. This finding establishes recognition not limited normal structures In conclusion, delineation functionally structurally highlights potential vaccine therapeutic candidates for COVID-19.

Language: Английский

Citations

36
Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike DOI Creative Commons
Timothy J.C. Tan, Abhishek Kumar Verma, Abby Odle

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(15)

Published: April 1, 2024

Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding spike protein. In contrast, whether antigenic occurs S2 remains largely elusive. Here, we perform a deep mutational scanning experiment to identify that affect three apex public antibodies. Our results indicate spatially diverse mutations, including D950N Q954H, which are observed Delta Omicron variants, respectively, weaken these Although antibodies known be nonneutralizing, show they confer protection vivo through Fc-mediated effector functions. Overall, this study indicates can undergo drift, represents potential challenge for development more universal coronavirus vaccines.

Language: Английский

Citations

9
An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies DOI
Yiquan Wang, Huibin Lv, Qi Wen Teo

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(10), P. 2453 - 2465.e7

Published: Aug. 19, 2024

Language: Английский

Citations

9
Broadly neutralizing antibodies targeting pandemic GII.4 variants or seven GII genotypes of human norovirus DOI
Juyeon Park, Lisa C. Lindesmith, Adam S. Olia

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(788)

Published: March 5, 2025

Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design broadly protective immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics quantitatively characterize circulating serum IgG repertoire before after immunization with an experimental monovalent GII.4 VP1 capsid-encoding adenoviral vaccine. Two participants were specifically selected basis breadth neutralization responses either across variants (participant A) or GII genotypes B). In participant A, vaccination back-boosted highly abundant antibody clonotypes targeting among rapidly evolving spanning from strain identified in 1987 2019. B, recall response consisting monoclonal antibodies remarkable cross-GII ligand-binding blockade (blocking ≥ seven genotypes) virus breadth. The cocrystal structure one these antibodies, VX22, complex capsid protruding (P) domain revealed epitope (residues 479 484 509 513) within two lateral loops P1 subdomain. Antibody evolutionary trajectory analysis further that VX22 had originally evolved early heterologous infection, likely by GII.12 strain. Together, our study demonstrates human broad potency can be boosted vector-based vaccine, findings may guide immunogens for vaccines.

Language: Английский

Citations

1
Convergent and clonotype-enriched mutations in the light chain drive affinity maturation of a public antibody DOI Creative Commons

Vishal U.S. Rao,

Iden A. Sapse, Hallie Cohn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

SUMMARY Public antibodies that recognize conserved epitopes are critical for vaccine development, and identifying somatic hypermutations (SHMs) enhance antigen affinity in these public responses is key to guiding design better protection. We propose affinity-enhancing SHMs selectively enriched antibody clonotypes, surpassing the background frequency seen carrying same V genes, but with different epitope specificities. Employing a human IGHV4-59 / IGKV3-20 as model, we compare SHM signatures also using recognizing other epitopes. Critically, this comparison identified clonotype-enriched mutations light chain. Our analyses show SHMs, combination, binding previously uncharacterized viral epitope, it increasing after multiple vaccinations. findings offer framework based on convergence clonotype-enrichment can help guide aimed elicit antibodies. Graphical Abstract Highlights Clonotype-enriched chain of antibody, M15 These targets undescribed, Serum levels targeting increase repeated vaccinations

Language: Английский

Citations

1
spa typing of methicillin-resistant Staphylococcus aureus isolated from domestic animals and veterinary staff in the UK and Ireland DOI Open Access
Arshnee Moodley, Marc Stegger, Arzu Funda BAĞCIGİL

et al.

Journal of Antimicrobial Chemotherapy, Journal Year: 2006, Volume and Issue: 58(6), P. 1118 - 1123

Published: Oct. 10, 2006

Region X of the protein A gene (spa) was sequenced from methicillin-resistant Staphylococcus aureus (MRSA) isolates originating animals, humans and environment at veterinary hospitals in UK Ireland. MRSA transmission between animals staff assessed on basis spa typing, PFGE epidemiological data.MRSA dogs (n = 27), horses 9), cats 6), 22) environmental surfaces 3) were analysed by typing. Known contacts human animal carriers ascertained hospitals.All feline, most canine (96%) (82%) showed profiles that either indistinguishable (subtype A1) or closely related (subtypes A2-A10) to epidemic clone EMRSA-15 (CC22), whereas equine (88%) CC8 (types C, D, E G). polymorphism enabled discrimination among strains assigned same type. Fifteen types clustering into two distinct groups detected, with t032 being prevalent (48%). The isolated seven members as those infected attended staff.Irrespective geographical origin, small generally clustered clonal complexes, CC22, respectively. combined use typing allowed better than each method used individually, provided useful information individuals.

Language: Английский

Citations

148
Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool DOI
Timm Weber,

Sabrina Dähling,

S. Rose

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(89)

Published: Nov. 17, 2023

The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond repeated antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory cell pool. We demonstrate that subsequent infection substantially increases frequency encoding SARS-CoV-2-neutralizing antibodies. However, this is not primarily attributable maturation, but selection preexisting clones. Moreover, broadly reactive arose early even neutralized highly mutated variants like XBB.1.5 individuals had encountered. Together, our data show immunity largely imprinted on over course multiple contacts can new through diversity.

Language: Английский

Citations

21