Complete escape of SARS-CoV-2 from dual monoclonal antibody therapy in a patient with acquired immunodeficiency
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB54706 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| day_0_isolate_passage_1.fasta.gz | Fasta.gz | |||
| day_0_isolate_passage_1_chrm_list.txt.gz | Txt | |||
| day_0_isolate_passage_2.fasta.gz | Fasta.gz | |||
| day_0_isolate_passage_2_chrm_list.txt.gz | Txt | |||
| day_0_swab.fasta.gz | Fasta.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patient with hypogammaglobulinemia. Following mAb treatment, the patient did not clear the infection. During viral persistence, SARS-CoV-2 acquired three novel spike mutations. Neutralization and mouse protection analyses demonstrate a complete viral escape from REGN-COV at the expense of ACE-2 binding. Final clearance of the virus occurred upon reduction of the immunosuppressive regimen and total IgG substitution. Serology suggests that the development of highly neutralizing IgM rather than IgG substitution aids clearance. Our findings emphasise that selection pressure by mAbs on SARS-CoV-2 can lead to development of escape variants in immunocompromised patients. Thus, modification of immunosuppressive therapy, if possible, might be preferable to control and clearance of the viral infection.
| S-EPMC10085998 | biostudies-literature
Project description:Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for coronavirus disease 2019 (COVID-19). However, ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can render monoclonal antibodies ineffective. Here, we completely map all of the mutations to the SARS-CoV-2 spike receptor-binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escapes LY-CoV016). In addition, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to the antigenic evolution of SARS-CoV-2.
| S-EPMC8020059 | biostudies-literature
Project description:Monoclonal antibodies and antibody cocktails are a promising therapeutic and prophylaxis for COVID-19. However, ongoing evolution of SARS-CoV-2 can render monoclonal antibodies ineffective. Here we completely map all mutations to the SARS-CoV-2 spike receptor binding domain (RBD) that escape binding by a leading monoclonal antibody, LY-CoV555, and its cocktail combination with LY-CoV016. Individual mutations that escape binding by each antibody are combined in the circulating B.1.351 and P.1 SARS-CoV-2 lineages (E484K escapes LY-CoV555, K417N/T escape LY-CoV016). Additionally, the L452R mutation in the B.1.429 lineage escapes LY-CoV555. Furthermore, we identify single amino acid changes that escape the combined LY-CoV555+LY-CoV016 cocktail. We suggest that future efforts should diversify the epitopes targeted by antibodies and antibody cocktails to make them more resilient to antigenic evolution of SARS-CoV-2.
| S-EPMC7924270 | biostudies-literature
Project description:Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments. Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting.
| S-EPMC8179113 | biostudies-literature
Project description:We generated LNP-mRNA encoding B.1.1.529 SARS-CoV-2 spike, and intramuscularly administered it in a human IgG and IgK knock-in mouse. Single cell VDJ-seq unveiled the sequences of human monoclonal antibodies targeting the B.1.1.529 SARS-CoV-2 spike protein.
2022-07-01 | GSE203030 | GEO
Project description:Convalescent sera of RT-PCR SARS-CoV-2 confirmed hospitalised patients were tested on the protein array to profile IgG, IgM, and IgA antibody levels against human coronaviruses.
2022-03-08 | E-MTAB-11523 | biostudies-arrayexpress
Project description:Class 1 and 2 monoclonal antibodies inhibit SARS-CoV-2 entry by blocking the interaction of the viral receptor-binding domain with angiotensin-converting enzyme 2 (ACE2), while class 3 antibodies target a highly conserved epitope outside the ACE2 binding site. We aimed to investigate the plasticity of the spike protein by propagating wild-type SARS-CoV-2 in the presence of class 3 antibody S309. After 12 weeks, we obtained a viral strain that was completely resistant to inhibition by S309, due to successively evolving amino acid exchanges R346S and P337L located in the paratope of S309. The antibody lost affinity to receptor-binding domains carrying P337L or both amino acid exchanges, while ACE2 binding was not affected. The resistant strain replicated efficiently in human CaCo-2 cells and was more susceptible to inhibition of fusion than the original strain. Overall, SARS-CoV-2 escaped inhibition by class 3 antibody S309 through a slow, but targeted evolution enabling immune escape and altering cell entry. This immune-driven enhancement of infectivity and pathogenicity could play an important role in the future evolution of SARS-CoV-2, which is under increasing immunological pressure from vaccination and previous infections.
| S-EPMC9449809 | biostudies-literature
Project description:De novo protein sequencing is one of the key problems in mass spectrometry-based proteomics, especially for novel proteins such as monoclonal antibodies for which genome information is often limited or not available. However, due to limitations in peptides fragmentation and coverage, as well as ambiguities in spectra interpretation, complete de novo assembly of unknown protein sequences still remains challenging. To address this problem, we propose an integrated system, ALPS, which for the first time can automatically assemble full-length monoclonal antibody sequences. Our system integrates de novo sequencing peptides, their quality scores and error-correction information from databases into a weighted de Bruijn graph to assemble protein sequences. We evaluated ALPS performance on two antibody data sets, each including a heavy chain and a light chain. The results show that ALPS was able to assemble three complete monoclonal antibody sequences of length 216-441 AA, at 100% coverage, and 96.64-100% accuracy.
| S-EPMC4999880 | biostudies-other
Project description:The molecular mechanisms that control the ordered patterning of vascular tissue development in plant are not well understood. Several models propose a two component for plant vascular differentiation in which requires both an inducer of vascular tissue an also an inhibitory component that prevents the formation of vascular bundles near pre-existing bundles by a process often termed lateral inhibition. We have identified two recessive allelic mutants in Arabidopsis, designated continuous vascular (cov-1, cov-2), which display a dramatic increase in vascular tissue in the stem in place of the interfascicular region that normally separates the vascular bundles. The mutant plants exhibited normal vascular patterning in leaves and cotyledons. Analysis of the interaction of cov with known auxin signalling mutant and direct analysis of auxin concentrations suggests that cov affects vascular pattering by some mechanism that is independent of auxin. COV is expressed in all plant tissue but more highly in developing flowers and stems. The COV protein is predicted to be an integral membrane protein of unknown function, conserved in both plants and bacteria that is involved in negatively regulating the differentiation of the vascular tissue in the stem of Arabidopsis.The phenotype of COV exhibits some similarities to acl5 which is known to be a defect in the gene for spermidine synthase. Consequently, we are interested to test the idea that COV may be involved in the transport or perception of polyamines and that polyamines may be essential signals in normal vascular tissue development. Clearly, it this proves to be the case we would expect to see some differences in the transcript levels of genes associated with these pathways. Experimenter name = Simon Turner; Experimenter phone = 0161 275 5751; Experimenter fax = 0161 275 3938; Experimenter address = University of Manchester; Experimenter address = School of Biological Sciences; Experimenter address = 3.614 Stopford building; Experimenter address = Oxford Rd; Experimenter address = Manchester; Experimenter zip/postal_code = M13 9PT; Experimenter country = UK Experiment Overall Design: 8 samples were used in this experiment
2008-06-14 | E-GEOD-5729 | biostudies-arrayexpress
Project description:Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
| S-EPMC7676316 | biostudies-literature