PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection
PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection
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DOI：
10.1021/acs.molpharmaceut.7b00118
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发表时间：
2017-07-01
影响因子：
4.9
通讯作者：
Andrianov, Alexander K.
中科院分区：
文献类型：
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作者：
Cayatte, Corinne;Marin, Alexander;Andrianov, Alexander K.
呼吸道合胞病毒融合后糖蛋白（RSVsF）是一种具有特异性的疫苗候选物，PCPP是一种结构明确的聚磷腈大分子，已被研究用作RSVsF的免疫佐剂。我们证明RSV sF-PCPP制剂诱导对RSV的高中和滴度，即使在低PCPP剂量下也与明矾制剂相当，并保护动物免受肺和上呼吸道中的病毒攻击。PCPP制剂的特征还在于Th 1偏向性应答，与单独的RSV sF或RSV sF明矾制剂更典型的Th 2偏向性应答相比，这表明聚磷酸酯佐剂的固有免疫刺激活性。我们将这些免疫活性RSVsF-PCPP制剂定义为具有不同物理化学参数的自组装水溶性蛋白质-聚合物复合物。在自发水性自组装过程中，复合物中蛋白质的二级结构和抗原性完全保留。这些发现进一步推进了cif聚磷腈免疫佐剂作为独特的双功能佐剂在一个水溶性分子中整合了递送和免疫刺激模式的概念。
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), Which is an attractive vaccine candid-ate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV Comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF alum formulations, suggesting an inherent immunostimulating activity of the polyphosphatene adjuvant. We defined these immunologically active RSV sF- PCPP formulations as self-asSembled water-Soluble protein-polymer complexes with distinct physicochemical-parameters The secondary structure and antigenicity of the protein in the complex were fully preserved during the spontaneous aqueous self assembly process. These findings further advance the concept cif polyphosphazene immunoadjuvants as unique dual-functionality adjuvants integrating delivery and immunostimulating modalities in one water-soluble molecule.