A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.
A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.
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DOI：
10.3389/fimmu.2022.941865
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
呼吸道合胞病毒(RSV)和人类偏肺病毒(HMPV)是引起儿童、老年人和免疫功能低下患者严重呼吸道感染的两个主要原因。融合(F)蛋白是中和抗体的主要靶点。在稳定融合前F蛋白构象和识别免疫优势表位方面的最新进展导致了许多融合前RSV F疫苗的临床试验。我们设计并测试了含有RSV F和hMPV F(rHMS-1)免疫优势表位的嵌合融合蛋白的免疫原性和保护效果。与融合前RSV F或hMPV F疫苗相比，RHMS-1有几个优势，包括专注于召回B细胞到最重要的保护性表位，以及能够用单一抗原诱导对两种病毒的保护。RHMS-1是一种三聚体重组蛋白，负染电子显微镜分析表明该蛋白与融合前的构象相似。用一组RSV和hMPV F特异性单抗对RHMS-1的抗原性进行了检测，发现该蛋白保留了这两种病毒的特征，包括RSV F的融合前表位。用rHMS-1免疫的小鼠产生了针对这两种病毒的中和抗体，并完全抵抗RSV或hMPV的攻击。总体而言，这项研究证明了对具有单一抗原的两种病毒的保护作用，并支持在其他临床前动物模型中测试RHMS-1。
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.
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DOI：
10.1093/infdis/jit839
发表时间：
2014-06-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Falsey AR;McElhaney JE;Beran J;van Essen GA;Duval X;Esen M;Galtier F;Gervais P;Hwang SJ;Kremsner P;Launay O;Leroux-Roels G;McNeil SA;Nowakowski A;Richardus JH;Ruiz-Palacios G;St Rose S;Devaster JM;Oostvogels L;Durviaux S;Taylor S
通讯作者：
Taylor S
影响因子：
--
作者：
CHANOCK, R;FINBERG, L
通讯作者：
FINBERG, L
影响因子：
16.6
作者：
Battles, Michael B.;Mas, Vicente;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
5.4
作者：
Bar-Peled, Yael;Diaz, Darren;Mousa, Jarrod J.
通讯作者：
Mousa, Jarrod J.
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P