Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53711, USA.
Vaccine. 2012 Nov 6;30(48):6871-7. doi: 10.1016/j.vaccine.2012.09.007. Epub 2012 Sep 16.
Currently available influenza vaccines provide suboptimal protection. In order to improve the quality of protective immune responses elicited following vaccination, we developed an oil-in-water nanoemulsion (NE)-based adjuvant for an intranasally-delivered inactivated influenza vaccine. Using a prime-boost vaccination regimen, we show that intranasal vaccines containing the W(80)5EC NE elicited higher titers of serum hemagglutination inhibiting (HAI) antibody and influenza-specific IgG and IgA titers compared to vaccines that did not contain the NE. Similarly, vaccines containing the W(80)5EC NE resulted in higher influenza-specific IgA levels in the bronchoalveolar lavage (BAL) fluid and nasal wash when compared to vaccines formulated without NE. The higher antibody titers in mice immunized with the NE-containing vaccines correlated with reduced viral loads in the lungs and nasal turbinates following a high dose viral challenge. Mice immunized with vaccines containing the W(80)5EC NE also showed a reduction in body weight loss following challenge compared to mice immunized with equivalent vaccines produced without NE. Taken together, our results show that the W(80)5EC NE substantially improves the magnitude of protective influenza-specific antibody responses and is a promising mucosal adjuvant for influenza vaccines and vaccines against other mucosal pathogens.
目前可用的流感疫苗提供的保护作用并不理想。为了提高接种疫苗后产生的保护性免疫反应的质量,我们开发了一种基于水包油纳米乳(NE)的佐剂,用于鼻内递送的灭活流感疫苗。通过初免-加强免疫方案,我们发现含有 W(80)5EC NE 的鼻内疫苗比不含 NE 的疫苗能诱导更高滴度的血清血凝抑制(HAI)抗体和流感特异性 IgG 和 IgA 滴度。同样,与不含 NE 的疫苗相比,含有 W(80)5EC NE 的疫苗在支气管肺泡灌洗液(BAL)和鼻冲洗液中诱导产生更高水平的流感特异性 IgA。用含有 NE 的疫苗免疫的小鼠的抗体滴度较高,与高剂量病毒攻毒后肺部和鼻甲骨中的病毒载量降低相关。与用不含 NE 的等效疫苗免疫的小鼠相比,用含有 W(80)5EC NE 的疫苗免疫的小鼠在攻毒后体重减轻也有所减少。总之,我们的结果表明,W(80)5EC NE 可显著提高保护性流感特异性抗体反应的幅度,是流感疫苗和针对其他粘膜病原体疫苗的有前途的粘膜佐剂。