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RV144 HIV-1 疫苗接种对感染后抗体反应产生影响。

RV144 HIV-1 vaccination impacts post-infection antibody responses.

机构信息

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.

出版信息

PLoS Pathog. 2020 Dec 8;16(12):e1009101. doi: 10.1371/journal.ppat.1009101. eCollection 2020 Dec.

Abstract

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

摘要

RV144 疫苗功效临床试验显示,HIV-1 感染减少了 31%。疫苗功效与对 HIV 包膜 (Env) V1V2 区域更强的结合抗体反应相关,随着反应减弱,功效降低。高水平的抗体依赖性细胞细胞毒性 (ADCC) 以及Env 特异性 IgA 的低血浆水平也与降低感染风险相关。我们研究了 RV144 疫苗接种是否会影响感染后 HIV-1 的功能性抗体反应。在 HIV 诊断后 6、12 和 36 个月,评估了 37 名疫苗接种者和 63 名安慰剂接受者的抗体反应。与安慰剂接受者相比,感染后 RV144 疫苗接种者的抗体反应的幅度、特异性、动力学、亚类识别和分布不同。疫苗接种者表现出对 V1V2 的 IgG1 结合特异性增加,以及 IgG2 和 IgG4 的增加,但对 HIV-1 Env 的 IgG3 减少。感染后,疫苗接种者和安慰剂接受者之间对 HIV-1 Env 的 IgA 结合没有差异。RV144 疫苗接种限制了感染后广泛中和抗体的发展,但增强了 Fc 介导的效应功能,表明 RV144 疫苗接种对 B 细胞的启动影响了下游抗体功能。然而,这些功能反应与疾病进展的临床标志物无关。这些数据表明,RV144 疫苗接种在 HIV-1 感染后对特定的结合和功能性抗体反应进行了 B 细胞的预刺激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc3/7748270/d35b1514e6b8/ppat.1009101.g001.jpg

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