دورية أكاديمية
أعرض في EDS

Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies.

التفاصيل البيبلوغرافية
العنوان: Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies.
المؤلفون: Diskin R; Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. ron.diskin@weizmann.ac.il, Klein F, Horwitz JA, Halper-Stromberg A, Sather DN, Marcovecchio PM, Lee T, West AP Jr, Gao H, Seaman MS, Stamatatos L, Nussenzweig MC, Bjorkman PJ
المصدر: The Journal of experimental medicine [J Exp Med] 2013 Jun 03; Vol. 210 (6), pp. 1235-49. Date of Electronic Publication: 2013 May 27.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Rockefeller University Press
مواضيع طبية MeSH: Antibodies, Neutralizing/*immunology , HIV Antibodies/*immunology , HIV Infections/*immunology , HIV-1/*immunology, AIDS Vaccines/genetics ; AIDS Vaccines/immunology ; Animals ; Antibodies, Neutralizing/genetics ; Cell Line ; HEK293 Cells ; HIV Antibodies/genetics ; HIV Envelope Protein gp120/genetics ; HIV Envelope Protein gp120/immunology ; HIV Infections/genetics ; HIV-1/genetics ; Humans ; Mice ; Mutation/genetics ; Mutation/immunology ; Structure-Activity Relationship
مستخلص: Recently identified broadly neutralizing antibodies (bNAbs) that potently neutralize most HIV-1 strains are key to potential antibody-based therapeutic approaches to combat HIV/AIDS in the absence of an effective vaccine. Increasing bNAb potencies and resistance to common routes of HIV-1 escape through mutation would facilitate their use as therapeutics. We previously used structure-based design to create the bNAb NIH45-46(G54W), which exhibits superior potency and/or breadth compared with other bNAbs. We report new, more effective NIH45-46(G54W) variants designed using analyses of the NIH45-46-gp120 complex structure and sequences of NIH45-46(G54W)-resistant HIV-1 strains. One variant, 45-46m2, neutralizes 96% of HIV-1 strains in a cross-clade panel and viruses isolated from an HIV-infected individual that are resistant to all other known bNAbs, making it the single most broad and potent anti-HIV-1 antibody to date. A description of its mechanism is presented based on a 45-46m2-gp120 crystal structure. A second variant, 45-46m7, designed to thwart HIV-1 resistance to NIH45-46(G54W) arising from mutations in a gp120 consensus sequence, targets a common route of HIV-1 escape. In combination, 45-46m2 and 45-46m7 reduce the possible routes for the evolution of fit viral escape mutants in HIV-1YU-2-infected humanized mice, with viremic control exhibited when a third antibody, 10-1074, was added to the combination.
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معلومات مُعتمدة: UM1 AI100663 United States AI NIAID NIH HHS; P01 AI100148 United States AI NIAID NIH HHS; R01AI081625 United States AI NIAID NIH HHS; UM1AI100663 United States AI NIAID NIH HHS; T32 GM007739 United States GM NIGMS NIH HHS; R01 AI081625 United States AI NIAID NIH HHS; P01AI100148 United States AI NIAID NIH HHS
سلسلة جزيئية: PDB 4JKP
المشرفين على المادة: 0 (AIDS Vaccines)
0 (Antibodies, Neutralizing)
0 (HIV Antibodies)
0 (HIV Envelope Protein gp120)
0 (gp120 protein, Human immunodeficiency virus 1)
تواريخ الأحداث: Date Created: 20130529 Date Completed: 20131112 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3674693
DOI: 10.1084/jem.20130221
PMID: 23712429
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-9538
DOI:10.1084/jem.20130221