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Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.

Cell. 2019-05; 
CirelliKimberly M,CarnathanDiane G,NogalBartek,MartinJacob T,RodriguezOscar L,UpadhyayAmit A,EnemuoChiamaka A,GebruEtse H,ChoeYury,VivianoFederico,NakaoCatherine,PauthnerMatthias G,ReissSamantha,CottrellChristopher A,SmithMelissa L,BastidasRaiza,GibsonWilliam,WolabaughAmber N,MeloMariane B,CossetteBenjamin,KumarVenkatesh,PatelNirav B,TokatlianTalar,MenisSergey,KulpDaniel W,BurtonDennis R,MurrellBen,SchiefWilliam R,BosingerSteven E,WardAndrew B,WatsonCorey T,SilvestriGuido,IrvineDarrell J,CrottyS
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Codon Optimization The heavy and light chains of the BDA monoclonal antibodies were codon-optimized, synthesized and cloned into pFUSE2ss-CHIghG1 and pFUSE2ss-CLIg-hl2, respectively, by GenScript. Antibodies were expressed and purified by GenScript. Get A Quote

摘要

Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (T) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential ... More

关键词

FNA,GC- T(FH),HIV vaccine,affinity maturation,immune complexes,memory B cells,non-human primates,rhesus macaque genome,somatic hypermuta
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