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Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques.
Cell Reports ( IF 8.8 ) Pub Date : 2020-09-08 , DOI: 10.1016/j.celrep.2020.108122
Fangzhu Zhao 1 , Collin Joyce 1 , Alison Burns 1 , Bartek Nogal 2 , Christopher A Cottrell 2 , Alejandra Ramos 3 , Trevor Biddle 1 , Matthias Pauthner 1 , Rebecca Nedellec 1 , Huma Qureshi 3 , Rosemarie Mason 4 , Elise Landais 3 , Bryan Briney 5 , Andrew B Ward 6 , Dennis R Burton 7 , Devin Sok 3
Affiliation  

BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a “public clonotype” that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.



中文翻译:

在免疫和感染的猕猴中将中和抗体的抗原决定簇特异性定​​位到HIV Env Trimer。

BG505 SOSIP是一个特性良好的近天然重组HIV信封(Env)三聚体,有望在连续HIV免疫原方案中诱导广泛中和抗体(bnAbs)。猕猴被认为是监测抗体(Ab)反应的最合适的临床前动物模型。因此,我们在这里报告从SOSIP免疫和BG505 SHIV感染的猕猴中分离出45种具有多种特异性的BG505自体中和抗体(nAbs)。我们将最有效的中和与两个表位相关联:C3 / V5和V1 / V3区。我们表明,所有的nAb都与已知的bnAb表位紧密结合,因此可能在空间上阻碍bnAb的诱导。我们还确定了针对免疫显性C3 / V5 nAb表位的“公共克隆型”,这表明常见的抗体重排可能有助于确定对Env免疫原的体液反应。该结果突出了疫苗设计的重要考虑因素,以期预期BG505 SOSIP三聚体的临床试验结果。

更新日期:2020-09-09
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