VelcroVax: a "Bolt-On" Vaccine Platform for Glycoprotein Display.
VelcroVax: a "Bolt-On" Vaccine Platform for Glycoprotein Display.
复制标题
作者：
对疫苗的设计和制造采用不同的方法对于能够应对世界各地的需求和新出现的病原体至关重要。病毒样颗粒（vlp）构成了两种最成功的许可疫苗（针对乙型肝炎病毒[HBV]和人乳头瘤病毒）的基础。它们是通过病毒结构蛋白的重组表达产生的，这些结构蛋白组装成免疫原性纳米颗粒。VLP可以被修饰成呈递不相关的抗原，这里我们描述了一种通用的“螺栓连接”平台（称为VelcroVax），其中捕获的VLP和目标抗原分别产生。我们利用修饰的HBV核心（HBcAg） VLP，表面表达针对SUMO标签的高亲和力结合序列（Affimer），并使用它从沙粒病毒Junín病毒（JUNV）中捕获SUMO标记的gp1糖蛋白。利用该模型系统，我们首次解决了VelcroVax VLPs的高分辨率结构，并表明与非复合物病毒蛋白相比，VelcroVax- junv gp1复合物诱导了更好的体液免疫反应。我们建议可以对该系统进行修改，以提供一系列抗原，从而形成未来快速反应疫苗接种策略的基础。乙型肝炎核心蛋白（HBc）形成非传染性病毒样颗粒，可以修饰成捕获分子，允许适当标记的抗原结合在其表面。该系统可以进行调整，并为通用的“栓接”疫苗平台（称为VelcroVax）提供基础，该平台可以轻松快速地进行修改，以产生纳米颗粒候选疫苗。
Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and newly emerging pathogens. Virus-like particles (VLPs) form the basis of two of the most successful licensed vaccines (against hepatitis B virus [HBV] and human papillomavirus). They are produced by recombinant expression of viral structural proteins, which assemble into immunogenic nanoparticles. VLPs can be modified to present unrelated antigens, and here we describe a universal “bolt-on” platform (termed VelcroVax) where the capturing VLP and the target antigen are produced separately. We utilize a modified HBV core (HBcAg) VLP with surface expression of a high-affinity binding sequence (Affimer) directed against a SUMO tag and use this to capture SUMO-tagged gp1 glycoprotein from the arenavirus Junín virus (JUNV). Using this model system, we have solved the first high-resolution structures of VelcroVax VLPs and shown that the VelcroVax-JUNV gp1 complex induces superior humoral immune responses compared to the noncomplexed viral protein. We propose that this system could be modified to present a range of antigens and therefore form the foundation of future rapid-response vaccination strategies. IMPORTANCE The hepatitis B core protein (HBc) forms noninfectious virus-like particles, which can be modified to present a capturing molecule, allowing suitably tagged antigens to be bound on their surface. This system can be adapted and provides the foundation for a universal “bolt-on” vaccine platform (termed VelcroVax) that can be easily and rapidly modified to generate nanoparticle vaccine candidates.
登录
查看更多内容
影响因子：
4.8
作者：
Johrden L;Tenbusch M;Lietz R;Bonsmann MS;Niezold T;Wildner O;Bayer W
通讯作者：
Bayer W
Junín病毒发病机理和病毒复制。
DOI：
10.3390/v4102317
发表时间：
2012-10-19
期刊：
Viruses
影响因子：
--
作者：
Grant A;Seregin A;Huang C;Kolokoltsova O;Brasier A;Peters C;Paessler S
通讯作者：
Paessler S
影响因子：
30.3
作者：
Mahmutovic S;Clark L;Levis SC;Briggiler AM;Enria DA;Harrison SC;Abraham J
通讯作者：
Abraham J
影响因子：
5.9
作者：
Crispin M;Zeltina A;Zitzmann N;Bowden TA
通讯作者：
Bowden TA
DOI：
10.4269/ajtmh.1994.51.554
发表时间：
1994-11-01
影响因子：
3.3
作者：
MILLS, JN;ELLIS, BA;JAHRLING, PB
通讯作者：
JAHRLING, PB