Microparticle RSV Vaccines Presenting the G Protein CX3C Chemokine Motif in the Context of TLR Signaling Induce Protective Th1 Immune Responses and Prevent Pulmonary Eosinophilia Post-Challenge.
Microparticle RSV Vaccines Presenting the G Protein CX3C Chemokine Motif in the Context of TLR Signaling Induce Protective Th1 Immune Responses and Prevent Pulmonary Eosinophilia Post-Challenge.
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在TLR信号传导的背景下，呈现G蛋白CX3C趋化因子基序的微粒RSV疫苗会诱导保护性TH1免疫反应并防止促障后肺嗜酸性粒细胞。
DOI：
10.3390/vaccines10122078
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发表时间：
2022-12-05
期刊：
影响因子：
7.8
通讯作者：
Tripp RA
中科院分区：
文献类型：
--
作者：
Powell TJ;Jacobs A;Tang J;Cardenas E;Palath N;Daniels J;Boyd JG;Bergeron HC;Jorquera PA;Tripp RA
使用逐层微粒（LbL-MP）制造来产生呈现融合肽的合成疫苗，所述融合肽含有RSV G蛋白CX 3C趋化因子基序和RSV基质蛋白2（GM 2）的CD 8表位，具有或不具有共价连接的TLR 2激动剂（Pam3.GM2）。在不存在佐剂的情况下用GM 2或Pam 3. GM 2LbL-MP免疫BALB/c小鼠引发G特异性抗体应答和M2特异性CD 8 + T细胞应答。用RSV攻击后，用GM 2 LbL-MP疫苗免疫的小鼠在肺中产生Th 2偏向的免疫应答，支气管肺泡灌洗液（BAL）中IL-4、IL-5、IL-13和嗜酸性粒细胞活化趋化因子水平升高，嗜酸性粒细胞肺内流。相比之下，用Pam3.GM2 LbL-MP疫苗免疫的小鼠在RSV攻击后的BAL液中具有相当低至不可检测水平的Th 2细胞因子和趋化因子以及非常低数量的嗜酸性粒细胞。此外，与用GM 2 LbL-MP疫苗免疫的小鼠相比，用Pam3.GM2 LbL-MP免疫的小鼠在攻毒后BAL液中也具有更高水平的RSV G特异性IgG 2a和IgG 2b。虽然两种候选物在攻击后保护小鼠免受感染，如通过RSV斑块的减少或消除所证明的，但TLR 2激动剂的包含产生更有效的抗体应答、更大的保护和远离Th 2/嗜酸性粒细胞应答的明显转变。由于在20世纪60年代测试的福尔马林灭活RSV（FI-RSV）疫苗的失败已被假设部分是由于疫苗对宿主TLR接合的消除和随后病毒感染时的不适当的Th 2应答，因此这些发现强调了在初始暴露于RSV G CX 3C期间先天免疫应答的适当接合的重要性。
Layer-by-layer microparticle (LbL-MP) fabrication was used to produce synthetic vaccines presenting a fusion peptide containing RSV G protein CX3C chemokine motif and a CD8 epitope of the RSV matrix protein 2 (GM2) with or without a covalently linked TLR2 agonist (Pam3.GM2). Immunization of BALB/c mice with either GM2 or Pam3.GM2 LbL-MP in the absence of adjuvant elicited G-specific antibody responses and M2-specific CD8+ T-cell responses. Following challenge with RSV, mice immunized with the GM2 LbL-MP vaccine developed a Th2-biased immune response in the lungs with elevated levels of IL-4, IL-5, IL-13, and eotaxin in the bronchoalveolar lavage (BAL) fluid and a pulmonary influx of eosinophils. By comparison, mice immunized with the Pam3.GM2 LbL-MP vaccine had considerably lower to non-detectable levels of the Th2 cytokines and chemokines and very low numbers of eosinophils in the BAL fluid post-RSV challenge. In addition, mice immunized with the Pam3.GM2 LbL-MP also had higher levels of RSV G-specific IgG2a and IgG2b in the post-challenge BAL fluid compared to those immunized with the GM2 LbL-MP vaccine. While both candidates protected mice from infection following challenge, as evidenced by the reduction or elimination of RSV plaques, the inclusion of the TLR2 agonist yielded a more potent antibody response, greater protection, and a clear shift away from Th2/eosinophil responses. Since the failure of formalin-inactivated RSV (FI-RSV) vaccines tested in the 1960s has been hypothesized to be partly due to the ablation of host TLR engagement by the vaccine and inappropriate Th2 responses upon subsequent viral infection, these findings stress the importance of appropriate engagement of the innate immune response during initial exposure to RSV G CX3C.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.4049/jimmunol.181.10.6692
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castilow EM;Legge KL;Varga SM
通讯作者：
Varga SM
影响因子：
3.6
作者：
Chida-Nagai, Ayako;Sato, Hiroki;Takeda, Atsuhito
通讯作者：
Takeda, Atsuhito
影响因子：
5.5
作者：
Cyr, Sonya L.;Jones, Taff;Ward, Brian J.
通讯作者：
Ward, Brian J.
影响因子：
3.8
作者：
Chirkova, Tatiana;Lin, Songbai;Anderson, Larry J.
通讯作者：
Anderson, Larry J.