دورية أكاديمية
Prevalence and Significance of Substitutions in the Fusion Protein of Respiratory Syncytial Virus Resulting in Neutralization Escape From Antibody MEDI8897.
| العنوان: | Prevalence and Significance of Substitutions in the Fusion Protein of Respiratory Syncytial Virus Resulting in Neutralization Escape From Antibody MEDI8897. |
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| المؤلفون: | Zhu Q; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Lu B; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., McTamney P; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Palaszynski S; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Diallo S; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Ren K; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Ulbrandt ND; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Kallewaard N; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Wang W; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Fernandes F; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Wong S; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Svabek C; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Moldt B; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Esser MT; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Jing H; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland., Suzich JA; Department of Infectious Diseases-Vaccines, MedImmune, LLC, Gaithersburg, Maryland. |
| المصدر: | The Journal of infectious diseases [J Infect Dis] 2018 Jul 13; Vol. 218 (4), pp. 572-580. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| مواضيع طبية MeSH: | Amino Acid Substitution*, Antibodies, Neutralizing/*immunology , Antibodies, Viral/*immunology , Immunologic Factors/*pharmacology , Respiratory Syncytial Virus Infections/*virology , Respiratory Syncytial Virus, Human/*immunology , Viral Fusion Proteins/*immunology, Binding Sites ; Biological Products/pharmacology ; Crystallography, X-Ray ; Drug Resistance, Viral ; Gene Frequency ; Humans ; Immune Evasion ; Mutant Proteins/chemistry ; Mutant Proteins/genetics ; Mutant Proteins/immunology ; Neutralization Tests ; Prevalence ; Protein Conformation ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus, Human/genetics ; Respiratory Syncytial Virus, Human/isolation & purification ; United States/epidemiology ; Viral Fusion Proteins/chemistry ; Viral Fusion Proteins/genetics ; Virus Attachment/drug effects ; Virus Replication/drug effects |
| مستخلص: | Background: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children. To date, no vaccine is approved for the broad population of healthy infants. MEDI8897, a potent anti-RSV fusion antibody with extended serum half-life, is currently under clinical investigation as a potential passive RSV vaccine for all infants. As a ribonucleic acid virus, RSV is prone to mutation, and the possibility of viral escape from MEDI8897 neutralization is a potential concern. Methods: We generated RSV monoclonal antibody (mAb)-resistant mutants (MARMs) in vitro and studied the effect of the amino acid substitutions identified on binding and viral neutralization susceptibility to MEDI8897. The impact of resistance-associated mutations on in vitro growth kinetics and the prevalence of these mutations in currently circulating strains of RSV in the United States was assessed. Results: Critical residues identified in MARMs for MEDI8897 neutralization were located in the MEDI8897 binding site defined by crystallographic analysis. Substitutions in these residues affected the binding of mAb to virus, without significant impact on viral replication in vitro. The frequency of natural resistance-associated polymorphisms was low. Conclusions: Results from this study provide insights into the mechanism of MEDI8897 escape and the complexity of monitoring for emergence of resistance. |
| المشرفين على المادة: | 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) 0 (Biological Products) 0 (F protein, human respiratory syncytial virus) 0 (Immunologic Factors) 0 (Mutant Proteins) 0 (Viral Fusion Proteins) |
| تواريخ الأحداث: | Date Created: 20180405 Date Completed: 20190910 Latest Revision: 20190910 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1093/infdis/jiy189 |
| PMID: | 29617879 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1537-6613 |
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| DOI: | 10.1093/infdis/jiy189 |