Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
PLoS One. 2013 Sep 10;8(9):e74905. doi: 10.1371/journal.pone.0074905. eCollection 2013.
Nanoparticle vaccines were produced using layer-by-layer fabrication and incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle vaccines produced a neutralizing antibody response that inhibited RSV replication in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-γ secreting cells compared to controls following RSV challenge. Remarkably, RSV challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2-specific IL-4 and IFN-γ secreting T cells, and increased M2-specific H-2Kd-tetramer positive CD8(+) T cells in the lungs compared to controls. Cell type analysis showed vaccination was not associated with increased pulmonary eosinophilia following RSV challenge. These results demonstrate that vaccination of mice with the RSV G protein nanoparticle vaccines induces a potent neutralizing antibody response, increased G protein- and M2-specific T cell responses, and a reduction in RSV disease pathogenesis.
纳米颗粒疫苗采用层层组装的方法制备，并将包含 CX3C 趋化因子基序的呼吸道合胞病毒（RSV）G 蛋白多肽纳入其中。用 G 蛋白纳米颗粒疫苗免疫的 BALB/c 小鼠产生了中和抗体反应，可抑制 RSV 攻击后肺部的 RSV 复制。ELISPOT 分析显示，与对照组相比，在 RSV 攻击后，G 纳米颗粒疫苗接种的小鼠具有更高水平的 RSV G 蛋白特异性 IL-4 和 IFN-γ 分泌细胞。值得注意的是，与对照组相比，RSV G 蛋白纳米颗粒疫苗接种的小鼠在 RSV 攻击后肺部 RSV M2 特异性 IL-4 和 IFN-γ 分泌 T 细胞以及 M2 特异性 H-2Kd-四聚体阳性 CD8(+)T 细胞增加。细胞类型分析表明，接种疫苗后，在 RSV 攻击后肺部并没有出现嗜酸性粒细胞增多。这些结果表明，用 RSV G 蛋白纳米颗粒疫苗对小鼠进行疫苗接种可诱导出强大的中和抗体反应、增加 G 蛋白和 M2 特异性 T 细胞反应，并减少 RSV 疾病的发病机制。
