A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology.
A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology.
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DOI：
10.1016/j.vaccine.2013.11.032
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发表时间：
2014-03-14
期刊：
影响因子：
5.5
通讯作者：
Vogel, Stefanie N.
中科院分区：
文献类型：
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作者：
Blanco, Jorge C. G.;Boukhvalova, Marina S.;Pletneva, Lioubov M.;Shirey, Kari Ann;Vogel, Stefanie N.
我们先前证明，通过用轻度TLR 4激动剂和佐剂单磷酰脂质A（MPL）配制疫苗，可以完全消除棉鼠肌内接种FI-RSV批次100后与RSV感染相关的严重细胞因子风暴和病理学。尽管有了这一显著的改善，但疫苗未能阻止病毒在肺部的复制。由于MPL是一种弱TLR 4激动剂，我们假设其佐剂活性是通过调节呼吸道驻留巨噬细胞的先天免疫应答介导的。因此，我们开发了一种新的疫苗制剂，其中包含纯化的、杆状病毒表达的、部分纯化的、无锚RSV F蛋白，用合成MPL配制，经鼻内给予棉鼠，然后进行皮内加强。这种新的制剂和异源“初免/加强”给药途径导致与单独用F蛋白接种的动物中观察到的病毒滴度相比降低的病毒滴度。此外，通过该途径接种的动物在RSV感染后未显示出增强的肺部病理学证据。这表明MPL作为免疫调节剂，保护宿主免受疫苗增强的病理，并在通过异源初免/加强免疫方案施用时减少下呼吸道中的RSV复制。
We previously demonstrated that the severe cytokine storm and pathology associated with RSV infection following intramuscular vaccination of cotton rats with FI-RSV Lot 100 could be completely abolished by formulating the vaccine with the mild TLR4 agonist and adjuvant, monophosphoryl lipid A (MPL). Despite this significant improvement, the vaccine failed to blunt viral replication in the lungs. Since MPL is a weak TLR4 agonist, we hypothesized that its adjuvant activity was mediated by modulating the innate immune response of respiratory tract resident macrophages. Therefore, we developed a new vaccine preparation with purified, baculovirus expressed, partially purified, anchorless RSV F protein formulated with synthetic MPL that was administered to cotton rats intranasally, followed by an intradermal boost. This novel formulation and heterologous “prime/boost” route of administration resulted in decreased viral titers compared to that seen in animals vaccinated with F protein alone. Furthermore, animals vaccinated by this route showed no evidence of enhanced lung pathology upon RSV infection. This indicates that MPL acts as an immune modulator that protects the host from vaccine-enhanced pathology, and reduces RSV replication in the lower respiratory tract when administered by a heterologous prime/boost immunization regimen.
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DOI：
10.1126/science.1234914
发表时间：
2013-05-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McLellan JS;Chen M;Leung S;Graepel KW;Du X;Yang Y;Zhou T;Baxa U;Yasuda E;Beaumont T;Kumar A;Modjarrad K;Zheng Z;Zhao M;Xia N;Kwong PD;Graham BS
通讯作者：
Graham BS
影响因子：
3.8
作者：
Pletneva, Lioubov M.;Haller, Otto;Blanco, Jorge C. G.
通讯作者：
Blanco, Jorge C. G.
影响因子：
5.5
作者：
Boukhvalova, Marina S.;Prince, Gregory A.;Blanco, Jorge C. G.
通讯作者：
Blanco, Jorge C. G.
DOI：
10.1073/pnas.1115941109
发表时间：
2012-02-21
影响因子：
11.1
作者：
Magro, Margarita;Mas, Vicente;Palomo, Concepcion
通讯作者：
Palomo, Concepcion
影响因子：
5.5
作者：
HANCOCK, GE;SPEELMAN, DJ;HAHN, DJ
通讯作者：
HAHN, DJ