气候变化领域集成服务门户(CCPortal): The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat

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DOI	10.1073/pnas.2018027118
	The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat
	Montefiori D.C.; Filsinger Interrante M.V.; Bell B.N.; Rubio A.A.; Joyce J.G.; Shiver J.W.; LaBranche C.C.; Kim P.S.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	The HIV-1 gp41 N-heptad repeat (NHR) region of the prehairpin intermediate, which is transiently exposed during HIV-1 viral membrane fusion, is a validated clinical target in humans and is inhibited by the Food and Drug Administration (FDA)-approved drug enfuvirtide. However, vaccine candidates targeting the NHR have yielded only modest neutralization activities in animals; this inhibition has been largely restricted to tier-1 viruses, which are most sensitive to neutralization by sera from HIV-1–infected individuals. Here, we show that the neutralization activity of the well-characterized NHR-targeting antibody D5 is potentiated >5,000-fold in TZM-bl cells expressing FcγRI compared with those without, resulting in neutralization of many tier-2 viruses (which are less susceptible to neutralization by sera from HIV-1–infected individuals and are the target of current antibody-based vaccine efforts). Further, antisera from guinea pigs immunized with the NHR-based vaccine candidate (ccIZN36)3 neutralized tier-2 viruses from multiple clades in an FcγRI-dependent manner. As FcγRI is expressed on macrophages and dendritic cells, which are present at mucosal surfaces and are implicated in the early establishment of HIV-1 infection following sexual transmission, these results may be important in the development of a prophylactic HIV-1 vaccine. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	HIV-1 \| vaccine \| prehairpin intermediate \| gp41 \| Fc receptor
语种	英语
scopus关键词	antiserum; Fc receptor; glycoprotein gp 41; Human immunodeficiency virus vaccine; immunoglobulin Fc fragment; animal experiment; animal model; Article; binding affinity; controlled study; dendritic cell; female; guinea pig; human; Human immunodeficiency virus 1; Human immunodeficiency virus infection; macrophage; nonhuman; priority journal; protein expression; virus isolation; virus neutralization; virus transmission
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180996
作者单位	Department of Surgery, Duke University Medical Center, Durham, NC 27710, United States; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, United States; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, United States; Stanford Biophysics Program, StanfordUniversity School of Medicine, Stanford, CA 94305, United States; Stanford ChEM-H, Stanford University, Stanford, CA 94305, United States; Department of Molecular and CellularPhysiology, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Biology, Stanford University School of Humanities and Sciences, Stanford, CA 94305, United States; Vaccine Process Development, Merck & Co., Inc., West Point, PA 19486, United States; Department of Vaccine Basic Research, Merck ResearchLaboratories, West Point, PA 19486, United States; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, United States; Chan...
推荐引用方式 GB/T 7714	Montefiori D.C.,Filsinger Interrante M.V.,Bell B.N.,et al. The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat[J],2021,118(3).
APA	Montefiori D.C..,Filsinger Interrante M.V..,Bell B.N..,Rubio A.A..,Joyce J.G..,...&Kim P.S..(2021).The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Montefiori D.C.,et al."The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).