An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice
An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice
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DOI：
10.1186/1742-4933-9-21
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发表时间：
2012-10-02
影响因子：
7.9
通讯作者：
Lee, Sujin
中科院分区：
文献类型：
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作者：
Cherukuri, Anu;Stokes, Kate L.;Lee, Sujin
背景资料：呼吸道合胞病毒（RSV）在老年人中引起重大疾病，部分原因是免疫衰老损害了该人群对感染的保护性免疫反应。尽管以前和目前的努力，目前没有RSV疫苗许可用于婴儿或老年人。佐剂RSV亚单位疫苗有可能加强减弱的免疫应答，并减少RSV疾病的负担，在老年population.Results：我们使用了一个老年BALB/c小鼠模型，以评估免疫应答RSV融合（F）蛋白的存在和不存在的明矾佐剂。我们证明了用明矾佐剂化的RSV F蛋白免疫的老年BALB/c小鼠在用野生型（wt）RSV攻击后第4天具有显著降低的肺病毒滴度。在第27天测量的血清中和抗体滴度与年轻和老年接种小鼠中的保护相关，尽管老年小鼠中抗体滴度的幅度较低。与年轻小鼠不同，在老年小鼠中，明矾佐剂RSV F不诱导肺T（H）2型细胞因子或嗜酸性粒细胞浸润相比，non-adjuvanted F蛋白以下野生型RSV challenge.Conclusion：我们的研究表明，中和抗RSV抗体滴度与保护在年轻和老年BALB/c小鼠接种RSV F蛋白疫苗。与未加佐剂的F蛋白相比，F +明矾制剂在年轻和老年小鼠中介导更大的保护作用。然而，虽然明矾可以增强老年小鼠中的F特异性抗体应答，但它不能完全克服衰老免疫系统对RSV F抗原应答的能力降低。因此，我们的数据表明，可能需要更强的佐剂来预防免疫衰老人群中的RSV疾病，以实现保护性中和抗体和有效的T（H）1型细胞因子应答的适当平衡，同时沿着最小的肺免疫病理学。
Background: Respiratory Syncytial Virus (RSV) causes significant disease in the elderly, in part, because immunosenescence impairs protective immune responses to infection in this population. Despite previous and current efforts, there is no RSV vaccine currently licensed in infants or elderly adults. Adjuvanted RSV subunit vaccines have the potential to boost waning immune responses and reduce the burden of RSV disease in the elderly population.Results: We used an aged BALB/c mouse model to evaluate immune responses to RSV Fusion (F) protein in the absence and presence of an alum adjuvant. We demonstrate that aged BALB/c mice immunized with alum-adjuvanted RSV F protein had significantly reduced lung viral titers at day 4 following challenge with wild-type (wt) RSV. Serum neutralizing antibody titers measured on day 27 correlated with protection in both young and aged vaccinated mice, although the magnitude of antibody titers was lower in aged mice. Unlike young mice, in aged mice, alum-adjuvanted RSV F did not induce lung T(H)2-type cytokines or eosinophil infiltration compared to non-adjuvanted F protein following wt RSV challenge.Conclusion: Our studies demonstrate that neutralizing anti-RSV antibody titers correlate with protection in both young and aged BALB/c mice vaccinated with RSV F protein vaccines. The F + alum formulation mediated greater protection compared to the non-adjuvanted F protein in both young and aged mice. However, while alum can boost F-specific antibody responses in aged mice, it does not completely overcome the reduced ability of a senescent immune system to respond to the RSV F antigen. Thus, our data suggest that a stronger adjuvant may be required for the prevention of RSV disease in immunosenescent populations, to achieve the appropriate balance of protective neutralizing antibodies and effective T(H)1-type cytokine response along with minimal lung immunopathology.