当前位置: X-MOL 学术Sci. Transl. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality.
Science Translational Medicine ( IF 17.1 ) Pub Date : 2020-06-10 , DOI: 10.1126/scitranslmed.aaw9066
Sonia Maciejewski 1 , Tracy J Ruckwardt 2 , Kaitlyn M Morabito 2 , Bryant M Foreman 1 , Katherine E Burgomaster 1 , David N Gordon 1 , Rebecca S Pelc 1 , Christina R DeMaso 1 , Sung-Youl Ko 2 , Brian E Fisher 2 , Eun Sung Yang 2 , Deepika Nair 2 , Kathryn E Foulds 2 , John Paul Todd 2 , Wing-Pui Kong 2 , Vicky Roy 3 , Maya Aleshnick 1 , Scott D Speer 1 , Nigel Bourne 4 , Alan D Barrett 4 , Martha C Nason 5 , Mario Roederer 2 , Martin R Gaudinski 2 , Grace L Chen 2 , Kimberly A Dowd 1 , Julie E Ledgerwood 2 , Galit Alter 3 , John R Mascola 2 , Barney S Graham 2 , Theodore C Pierson 1
Affiliation  

The emergence of Zika virus (ZIKV) in the Americas stimulated the development of multiple ZIKV vaccine candidates. We previously developed two related DNA vaccine candidates encoding ZIKV structural proteins that were immunogenic in animal models and humans. We sought to identify neutralizing antibody (NAb) properties induced by each vaccine that correlated with protection in nonhuman primates (NHPs). Despite eliciting equivalent NAb titers in NHPs, these vaccines were not equally protective. The transfer of equivalent titers of vaccine-elicited NAb into AG129 mice also revealed nonequivalent protection, indicating qualitative differences among antibodies (Abs) elicited by these vaccines. Both vaccines elicited Abs with similar binding titers against envelope protein monomers and those incorporated into virus-like particles, as well as a comparable capacity to orchestrate phagocytosis. Functional analysis of vaccine-elicited NAbs from NHPs and humans revealed a capacity to neutralize the structurally mature form of the ZIKV virion that varied in magnitude among vaccine candidates. Conversely, sensitivity to the virion maturation state was not a characteristic of NAbs induced by natural or experimental infection. Passive transfer experiments in mice revealed that neutralization of mature ZIKV virions more accurately predicts protection from ZIKV infection. These findings demonstrate that NAb correlates of protection may differ among vaccine antigens when assayed using standard neutralization platforms and suggest that measurements of Ab quality, including the capacity to neutralize mature virions, will be critical for defining correlates of ZIKV vaccine-induced immunity.



中文翻译:

不同的中和抗体与相关寨卡病毒疫苗之间的保护相关,确定了抗体质量的作用。

美洲寨卡病毒(ZIKV)的出现刺激了多种ZIKV候选疫苗的发展。我们先前开发了两种相关的DNA候选疫苗,它们编码ZIKV结构蛋白,在动物模型和人类中具有免疫原性。我们试图确定由每种疫苗诱导的与非人类灵长类动物(NHP)中的保护作用相关的中和抗体(NAb)特性。尽管在NHP中引起了等效的NAb效价,但这些疫苗的保护作用不同。等效滴度的疫苗引起的NAb转移到AG129小鼠中也显示出不等效的保护作用,表明这些疫苗引起的抗体(Abs)之间的质量差异。两种疫苗均可针对包膜蛋白单体和掺入病毒样颗粒的抗体产生相似的结合效价,以及协调吞噬作用的能力。对来自NHP和人类的疫苗诱导的NAb的功能分析表明,具有中和ZIKV病毒体结构成熟形式的能力,该形式在候选疫苗之间的大小不同。相反,对病毒体成熟状态的敏感性不是自然或实验感染诱导的NAb的特征。小鼠的被动转移实验表明,成熟ZIKV病毒体的中和作用可以更准确地预测对ZIKV感染的保护作用。这些发现表明,使用标准中和平台进行分析时,疫苗抗原之间的NAb保护相关性可能有所不同,并表明对Ab质量的测量,包括中和成熟病毒体的能力,

更新日期:2020-06-10
down
wechat
bug