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HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.

Immunity. 2016; 
SteichenJon M,KulpDaniel W,TokatlianTalar,EscolanoAmelia,DosenovicPia,StanfieldRobyn L,McCoyLaura E,OzorowskiGabriel,HuXiaozhen,KalyuzhniyOleksandr,BrineyBryan,SchiffnerTorben,GarcesFernando,FreundNatalia T,GitlinAlexander D,MenisSergey,GeorgesonErik,KubitzMichael,AdachiYumiko,JonesMeaghan,MutafyanAndrew A,YunDong Soo,MayerChristian T,WardAndrew B,BurtonDennis R,WilsonIan A,IrvineDarrell J,NussenzweigMichel C,SchiefWilli
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Mutagenesis Services Genes were synthesized by GenScript. gp120s, gp140s, antigen binding fragments (Fabs), and IgGs were expressed in 293 cells and purified...The BG505 SOSIP whole-gene saturation mutagenesis and “rare” amino acid libraries were synthesized by Integrated DNA Technologies and GenScript, respectively. Get A Quote

摘要

Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 ... More

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