Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV
Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV
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DOI：
10.1128/jvi.78.11.6024-6032.2004
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Graham, BS
中科院分区：
文献类型：
--
作者：
Johnson, TR;Teng, MN;Graham, BS
在呼吸道合胞病毒（RSV）攻击后，用RSV G或用福尔马林灭活的RSV（FI-RSV）免疫的小鼠表现出与2型细胞因子产生和肺嗜酸性粒细胞增多相关的严重疾病。这导致了RSV G的存在是FI-RSV中诱导疾病增强性T细胞应答的因子的提议。因此，我们评估了RSV G及其免疫优势区在FI-RSV免疫期间诱导异常免疫应答中的作用。用野生型（wt）RSV或重组RSV（rRSV）的FI制备物免疫BALB/c小鼠，所述重组RSV含有（i）整个G基因、（ii）编码免疫显性区的氨基酸187至197的G基因区域或（iii）整个SH基因的缺失。攻毒后，测定疾病、RSV滴度、细胞因子水平和肺嗜酸性粒细胞增多症。用缺失病毒的FI制备物免疫的小鼠中，攻毒后RSV滴度峰值显著高于用FI-rRSV wt免疫的小鼠，表明FI-RSV中G或SH的缺失降低了其保护效力。相对于用FI-rRSV wt免疫的小鼠，G或其表位的缺失没有减少疾病、细胞因子产生或嗜酸性粒细胞增多。虽然细胞因子水平和嗜酸性粒细胞增多相似，但在用SH缺失的FI-RSV免疫的小鼠中疾病减少。这些数据表明，G特异性免疫应答对于疫苗诱导的保护可能是重要的，并且不仅仅是FI-RSV疫苗增强疾病的基础。这些数据表明，RSV抗原递送方法而不是蛋白质组成影响诱导的免疫应答的表型，并且RSV G不一定应从潜在的疫苗策略中排除。
Following respiratory syncytial virus (RSV) challenge, mice immunized with RSV G or with formalin-inactivated RSV (FI-RSV) exhibit severe disease associated with type 2 cytokine production and pulmonary eosinophilia. This has led to the proposal that the presence of RSV G is the factor in FI-RSV that induces disease-enhancing T-cell responses. Therefore, we evaluated the role of RSV G and its immunodominant region in the induction of aberrant immune responses during FI-RSV immunization. BALB/c mice were immunized with FI preparations of wild-type (wt) RSV or recombinant RSV (rRSV) containing deletions of (i) the entire G gene, (ii) the region of the G gene encoding amino acids 187 to 197 of the immunodominant region, or (iii) the entire SH gene. After challenge, illness, RSV titers, cytokine levels, and pulmonary eosinophilia were measured. Peak RSV titers postchallenge were significantly greater in mice immunized with FI preparations of the deletion viruses than in those immunized with FI-rRSV wt, suggesting that the absence of G or SH in FI-RSV reduced its protective efficacy. Deletion of G or its epitope did not reduce illness, cytokine production, or eosinophilia relative to that in mice immunized with FI-rRSV wt. While cytokine levels and eosinophilia were similar, illness was reduced in mice immunized with SH-deleted FI-RSV. These data suggest that G-specific immune responses may be important for vaccine-induced protection and are not solely the basis for FI-RSV vaccine-enhanced illness. These data suggest that the method of RSV antigen delivery, rather than the protein composition, influences the phenotype of the induced immune responses and that RSV G should not necessarily be excluded from potential vaccine strategies.