Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model.
Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model.
复制标题
DOI：
10.4161/hv.27383
复制
发表时间：
2014
影响因子：
4.8
通讯作者：
Baker JR Jr
中科院分区：
文献类型：
--
作者：
Passmore C;Makidon PE;O'Konek JJ;Zahn JA;Pannu J;Hamouda T;Bitko V;Myc A;Lukacs NW;Fattom A;Baker JR Jr
呼吸道合胞病毒 (RSV) 是一种普遍存在的病毒，几乎感染两岁以下的所有人，是婴儿、老年人和其他免疫系统受损的人呼吸道疾病的主要来源。目前没有可用的疫苗。先前使用福尔马林灭活 RSV (FI-RSV) 的努力与临床疫苗试验后病毒暴露后呼吸道疾病的加重有关。一些研究人员和制药公司已在临床前和临床研究中使用载体相关的减毒活 RSV 疫苗。然而，另一种有吸引力的方法是亚单位疫苗，它更容易生产和质量控制。我们的小组之前已经在小鼠感染模型中证明，用纳米乳剂灭活和佐剂RSV进行鼻内免疫可诱导体液和细胞免疫反应，从而防止RSV感染。目前的研究表征了由纳米乳剂辅助的鼻内 RSV F 蛋白引发的免疫反应。鼻内应用纳米乳剂佐剂 F 蛋白可诱导快速而强烈的全身和粘膜抗体反应，并针对随后的 RSV 攻击提供保护。重要的是，免疫动物的 RSV 攻击不会引起气道高反应性、Th2 倾斜的免疫反应或与福尔马林灭活疫苗过敏反应相关的免疫病理学。这些结果表明，以纳米乳剂佐剂的RSV F蛋白可能是一种良好的粘膜疫苗候选物。在纳米乳剂中配制 RSV F 蛋白可创建一种结构明确且控制良好的疫苗，可通过鼻内递送诱导 T 细胞介导的免疫，而不会诱发与 FI-RSV 疫苗接种和感染小鼠模型相关的疾病增强。
Respiratory Syncytial Virus (RSV) is a ubiquitous virus that infects almost all people by age two and is a major source of respiratory illness in infants, the elderly and others with compromised immune systems. Currently there is no available vaccine. Prior efforts using formalin-inactivated RSV (FI-RSV) were associated with enhanced respiratory disease upon viral exposure following clinical vaccine trials. Several researchers and pharmaceutical companies have utilized vector-associated live attenuated RSV vaccines in pre-clinical and clinical studies. Another attractive approach, however, is a subunit vaccine which would be easier to produce and quality control. Our group has previously demonstrated in a murine model of infection that intranasal immunization with nanoemulsion-inactivated and adjuvanted RSV induces humoral and cellular immune responses, resulting in protection against RSV infection. The present studies characterize the immune responses elicited by intranasal RSV F protein adjuvanted with nanoemulsion. Intranasal application of nanoemulsion adjuvanted F protein induced a rapid and robust systemic and mucosal antibody response, as well as protection against subsequent RSV challenge. Importantly, RSV challenge in immunized animals did not elicit airway hyper-reactivity, a Th2-skewed immune response or immunopathology associated with hypersensitivity reactions with formalin-inactivated vaccine. These results suggest that RSV F protein adjuvanted with nanoemulsion may be a good mucosal vaccine candidate. Formulating RSV F protein in nanoemulsion creates a well-defined and well-controlled vaccine that can be delivered intranasally to induce T cell mediated immunity without inducing enhanced disease associated with the mouse model of FI-RSV vaccination and infection.
登录
查看更多内容
影响因子：
3.7
作者：
Makidon, Paul E.;Bielinska, Anna U.;Baker, James R., Jr.
通讯作者：
Baker, James R., Jr.
影响因子：
5.4
作者：
Makidon, P. E.;Knowlton, J.;Baker, J. R., Jr.
通讯作者：
Baker, J. R., Jr.
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
影响因子：
7.9
作者：
Cherukuri, Anu;Stokes, Kate L.;Lee, Sujin
通讯作者：
Lee, Sujin
影响因子：
--
作者：
Hamouda, Tarek;Sutcliffe, Joyce A.;Baker, James R., Jr.
通讯作者：
Baker, James R., Jr.