Hancock G E, Heers K M, Smith J D, Scheuer C A, Ibraghimov A R, Pryharski K S
Department of Immunology Research, Wyeth-Lederle Vaccines, 211 Bailey Road, West Henrietta, NY 14586, USA.
Vaccine. 2001 Sep 14;19(32):4874-82. doi: 10.1016/s0264-410x(01)00228-6.
The feasibility of using oligodeoxynucleotides (ODN) containing unmethylated CpG motifs as parenteral adjuvants for subunit vaccines against RSV was tested in BALB/c mice. Compared with immunization with natural F protein adsorbed to aluminum hydroxide (F/AlOH) adjuvant alone, coadministration of F/AlOH with CpG ODN resulted in statistically significant increases in serum neutralization titers, an enhanced generation of splenic antigen-dependent killer cell precursors, and accelerated clearance of infectious virus from lungs 4 days after challenge. The statistically significant increases in serum IFNgamma and anti-F protein IgG2a titers, and significantly diminished pulmonary IL-5 and eosinophilia after challenge indicated that CpG ODN enhanced the ability of F/AlOH to elicit type 1 immune responses. F protein-specific serum IgE titers were also reduced. Further analysis of pulmonary inflammatory cells demonstrated an expansion of CD8(+) T cells, relative to the CD4(+) T cell compartment. The potency of CpG ODN was not adversely affected in gene knockout mice devoid of the p35 chain of the IL-12 heterodimer. Taken together, the results suggest a novel formulation for naïve recipients of F protein-based subunit vaccines that does not result in a type 2 phenotype.
在BALB/c小鼠中测试了使用含有未甲基化CpG基序的寡脱氧核苷酸(ODN)作为针对呼吸道合胞病毒(RSV)的亚单位疫苗的肠胃外佐剂的可行性。与单独用吸附于氢氧化铝(F/AlOH)佐剂的天然F蛋白免疫相比,F/AlOH与CpG ODN共同给药导致血清中和滴度在统计学上显著增加,脾抗原依赖性杀伤细胞前体的生成增强,并且在攻击后4天从肺中加速清除感染性病毒。攻击后血清IFNγ和抗F蛋白IgG2a滴度在统计学上显著增加,并且肺部IL-5和嗜酸性粒细胞显著减少,这表明CpG ODN增强了F/AlOH引发1型免疫反应的能力。F蛋白特异性血清IgE滴度也降低。对肺炎症细胞的进一步分析表明,相对于CD4(+) T细胞区室,CD8(+) T细胞有所扩增。在缺乏IL-12异二聚体p35链的基因敲除小鼠中,CpG ODN的效力未受到不利影响。综上所述,结果表明了一种针对基于F蛋白的亚单位疫苗初免接种者的新型配方,该配方不会导致2型表型。