Adjuvants influence the maturation of VRC01-like antibodies during immunization.

Adjuvants influence the maturation of VRC01-like antibodies during immunization.
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DOI:
10.1016/j.isci.2022.105473
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发表时间:
2022-11-18
期刊:
影响因子:
5.8
通讯作者:
Stamatatos, Leonidas
Stamatatos, Leonidas
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Knudsen, Maria L.;Agrawal, Parul;MacCamy, Anna;Parks, K. Rachael;Gray, Matthew D.;Takushi, Brittany N.;Khechaduri, Arineh;Salladay, Kelsey R.;Coler, Rhea N.;LaBranche, Celia C.;Montefiori, David;Stamatatos, Leonidas

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一旦表达种系vrc01类B细胞受体的幼稚B细胞被种系靶向免疫原激活,它们就会进入生发中心并经历亲和成熟。vrc01类抗体的完全成熟需要异源Envs加强免疫。在这里,我们研究了激活先天免疫系统不同途径的三种佐剂Poly(I:C)、GLA-LSQ或Rehydragel是否以及如何影响vrc01类bcr在被种系靶向426c.Mod激活后积累的体细胞突变的速率和类型。核心免疫原与异源HxB2.WT。核心增强免疫原。我们报道,虽然佐剂的使用对启动后血浆抗体反应的持久性没有影响,但它影响了增强后血浆VRC01抗体的滴度和诱导的VRC01抗体的体细胞突变的积累。VRC01 B细胞可被种系靶向HIV-1 Env免疫原在体内激活佐剂影响VRC01 B细胞的初始应答程度佐剂影响异源增强后血浆VRC01抗体滴度佐剂影响成熟VRC01 bcr的突变率和类型免疫反应;免疫学;病毒学。
Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether and how three adjuvants, Poly(I:C), GLA-LSQ, or Rehydragel, that activate different pathways of the innate immune system, influence the rate and type of somatic mutations accumulated by VRC01-class BCRs that become activated by the germline-targeting 426c.Mod.Core immunogen and the heterologous HxB2.WT.Core booster immunogen. We report that although the adjuvant used had no influence on the durability of plasma antibody responses after the prime, it influenced the plasma VRC01 antibody titers after the boost and the accumulation of somatic mutations on the elicited VRC01 antibodies. VRC01 B cells can be activated in vivo by a germline-targeting HIV-1 Env immunogen Adjuvants affect the magnitude of the initial VRC01 B cell response Adjuvants affect plasma VRC01 antibody titers following heterologous boosting Adjuvants affect the rate and type of mutations in maturing VRC01 BCRs Biological sciences; Immune response; Immunology; Virology.
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