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Emerging Microbes & Infections Volume 5, 2016 - Issue 1
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Non-neutralizing protective antibodies

An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene

Zhiwu SunKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Yun ZhuNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing100101, China
,
Qian WangKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Ling YeDepartment of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA30322, USA
,
Yanyan DaiKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Shan SuKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Fei YuKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Tianlei YingKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China
,
Chinglai YangDepartment of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA30322, USA
,
Shibo JiangKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, China;Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY10065, USACorrespondence[email protected]
&
Lu LuKey Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai200032, ChinaCorrespondence[email protected]
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Pages 1-12 | Received 07 May 2016, Accepted 07 Jun 2016, Published online: 25 Jan 2019

  • MurrayCJ,OrtbladKF,GuinovartCet al.Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet2014; 384:1005–1070.
  • JohnstonMI,FauciAS.HIV vaccine development—improving on natural immunity.N Engl J Med2011; 365:873–875.
  • WyattR,SodroskiJ.The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens.Science1998; 280:1884–1888.
  • PantophletR,BurtonDR.GP120: target for neutralizing HIV-1 antibodies.Annu Rev Immunol2006; 24:739–769.
  • DouekDC,KwongPD,NabelGJ.The rational design of an AIDS vaccine.Cell2006; 124:677–681.
  • KorberB,GaschenB,YusimKet al.Evolutionary and immunological implications of contemporary HIV-1 variation.Br Med Bull2001; 58:19–42.
  • WalkerBD,BurtonDR.Toward an AIDS vaccine.Science2008; 320:760–764.
  • PoignardP,MoulardM,GolezEet al.Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies.J Virol2003; 77:353–365.
  • CrooksET,MoorePL,FrantiMet al.A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120.Virology2007; 366:245–262.
  • ZhuP,LiuJ,BessJet al.Distribution and three-dimensional structure of AIDS virus envelope spikes.Nature2006; 441:847–852.
  • FlynnNM,ForthalDN,HarroCDet al.Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection.J Infect Dis2005; 191:654–665.
  • HuangJ,OfekG,LaubLet al.Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.Nature2012; 491:406–412.
  • MonteroM,van HoutenNE,WangXet al.The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design.Microbiol Mol Biol Rev2008; 72:54–84.
  • BruelT,Guivel-BenhassineF,AmraouiSet al.Elimination of HIV-1-infected cells by broadly neutralizing antibodies.Nat Commun2016; 7:10844.
  • Bouvin-PleyM,MorgandM,MeyerLet al.Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.J Virol2014; 88:13910–13917.
  • CardosoRM,ZwickMB,StanfieldRLet al.Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41.Immunity2005; 22:163–173.
  • CortiD,LanzavecchiaA.Broadly neutralizing antiviral antibodies.Annu Rev Immunol2013; 31:705–742.
  • KleinF,MouquetH,DosenovicPet al.Antibodies in HIV-1 vaccine development and therapy.Science2013; 341:1199–1204.
  • WalkerLM,HuberM,DooresKJet al.Broad neutralization coverage of HIV by multiple highly potent antibodies.Nature2011; 477:466–470.
  • CoëffierE,ClémentJ-M,CussacVet al.Antigenicity and immunogenicity of the HIV-1 gp41 epitope ELDKWA inserted into permissive sites of the MalE protein.Vaccine2000; 19:684–693.
  • EckhartL,RaffelsbergerW,FerkoBet al.Immunogenic presentation of a conserved gp41 epitope of human immunodeficiency virus type 1 on recombinant surface antigen of hepatitis B virus.J Gen Virol1996; 77:2001–2008.
  • JoyceJG,HurniWM,BoguskyMJet al.Enhancement of α-helicity in the HIV-1 inhibitory peptide DP178 leads to an increased affinity for human monoclonal antibody 2F5 but does not elicit neutralizing responses in vitro implications for vaccine design.J Biol Chem2002; 277:45811–45820.
  • LiangX,MunshiS,ShendureJet al.Epitope insertion into variable loops of HIV-1 gp120 as a potential means to improve immunogenicity of viral envelope protein.Vaccine1999; 17:2862–2872.
  • MarusicC,RizzaP,LattanziLet al.Chimeric plant virus particles as immunogens for inducing murine and human immune responses against human immunodeficiency virus type 1.J Virol2001; 75:8434–8439.
  • MusterT,GuineaR,TrkolaAet al.Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS.J Virol1994; 68:4031–4034.
  • KimM,QiaoZ,YuJet al.Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state.Vaccine2007; 25:5102–5114.
  • LawM,CardosoRM,WilsonIAet al.Antigenic and immunogenic study of membrane-proximal external region-grafted gp120 antigens by a DNA prime-protein boost immunization strategy.J Virol2007; 81:4272–4285.
  • YeL,WenZ,DongKet al.Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric protein-based DNA and VLP vaccines.PLoS One2011; 6:e14813.
  • MonteroM,GulzarN,KlaricKAet al.Neutralizing epitopes in the membrane-proximal external region of HIV-1 gp41 are influenced by the transmembrane domain and the plasma membrane.J Virol2012; 86:2930–2941.
  • SunZ-YJ,OhKJ,KimMet al.HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane.Immunity2008; 28:52–63.
  • ReardonPN,SageH,DennisonSMet al.Structure of an HIV-1–neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.Proc Natl Acad Sci USA2014; 111:1391–1396.
  • HeY,ChengJ,LuHet al.Potent HIV fusion inhibitors against Enfuvirtide-resistant HIV-1 strains.Proc Natl Acad Sci USA2008; 105:16332–16337.
  • LuL,PanC,LiYet al.A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains.Retrovirology2012; 9:104.
  • LuL,TongP,YuXet al.HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting different susceptibility to HIV fusion inhibitors with pocket-or membrane-binding domain.Biochim Biophys Acta2012; 1818:2950–2957.
  • HeY,LiuS,JingWet al.Conserved residue Lys574 in the cavity of HIV-1 Gp41 coiled-coil domain is critical for six-helix bundle stability and virus entry.J Biol Chem2007; 282:25631–25639.
  • YuX,LuL,CaiLet al.Mutations of Gln64 in the HIV-1 gp41 N-terminal heptad repeat render viruses resistant to peptide HIV fusion inhibitors targeting the gp41 pocket.J Virol2012; 86:589–593.
  • PanceraM,McLellanJS,WuXet al.Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1.J Virol2010; 84:8098–8110.
  • ParekhBS,BergerE,SibleySet al.Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay.MAbs2012; 4:310–318.
  • AlvarezRA,HamlinRE,MonroeAet al.HIV-1 Vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells.J Virol2014; 88:6031–6046.
  • ZhangY.I-TASSER server for protein 3D structure prediction.BMC Bioinformatics2008; 9:40.
  • BomselM,TudorD,DrilletASet al.Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges.Immunity2011; 34:269–280.
  • OfekG,TangM,SamborAet al.Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope.J Virol2004; 78:10724–10737.
  • CorreiaBE,BanY-EA,FriendDJet al.Computational protein design using flexible backbone remodeling and resurfacing: case studies in structure-based antigen design.J Mol Biol2011; 405:284–297.
  • CorreiaBE,BanY-EA,HolmesMAet al.Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope.Structure2010; 18:1116–1126.
  • OfekG,GuenagaFJ,SchiefWRet al.Elicitation of structure-specific antibodies by epitope scaffolds.Proc Natl Acad Sci USA2010; 107:17880–17887.
  • LiuW,ChenYH.High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins.Eur J Immunol2005; 35:505–514.
  • LiuW,PengZ,LiuZ.High epitope density in a single recombinant protein molecule of the extracellular domain of influenza A virus M2 protein significantly enhances protective immunity.Vaccine2004; 23:366–371.
  • HaynesBF,GilbertPB,McElrathMJet al.Immune-correlates analysis of an HIV-1 vaccine efficacy trial.N Engl J Med2012; 366:1275–1286.

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