Recombinant rabies viruses expressing GM-CSF or flagellin are effective vaccines for both intramuscular and oral immunizations.
Recombinant rabies viruses expressing GM-CSF or flagellin are effective vaccines for both intramuscular and oral immunizations.
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DOI：
10.1371/journal.pone.0063384
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fu ZF
中科院分区：
文献类型：
--
作者：
Zhou M;Zhang G;Ren G;Gnanadurai CW;Li Z;Chai Q;Yang Y;Leyson CM;Wu W;Cui M;Fu ZF
我们之前的研究表明，表达趋化因子或细胞因子（包括GM-CSF）的重组狂犬病病毒（rRABV）可以通过招募和/或激活树突状细胞（DC）来增强免疫原性。在这项研究中，细菌鞭毛蛋白被克隆到RABV基因组中，重组病毒LBNSE-鞭毛蛋白被拯救。为了比较 LBNSE-鞭毛蛋白与表达 GMCSF 的重组病毒 (LBNSE-GMCSF) 的免疫原性，通过肌内 (i.m) 或口服途径用这些 rRABV 免疫小鼠。不表达任何外源分子的亲本病毒（LBNSE）也被纳入进行比较。免疫后三周对肌内免疫的小鼠进行放血以测量病毒中和抗体(VNA)，然后用50LD50攻击病毒标准品(CVS-24)进行攻击。口服免疫的小鼠在三周后进行加强免疫，然后在加强免疫一周后放血并进行攻击。结果发现，LBNSE-GMCSF 和 LBNSE-鞭毛蛋白在外周募集/激活了更多的 DC 和 B 细胞，刺激了更高水平的适应性免疫反应 (VNA)，并在肌内和腹腔中比母体病毒 LBNSE 保护了更多的小鼠免受攻击感染。和口服免疫组。总之，这些研究表明，表达 GM-CSF 或鞭毛蛋白的重组 RABV 在肌内和体内均比亲本病毒更具免疫原性。和口服免疫接种。
Our previous studies indicated that recombinant rabies viruses (rRABV) expressing chemokines or cytokines (including GM-CSF) could enhance the immunogenicity by recruiting and/or activating dendritic cells (DC). In this study, bacterial flagellin was cloned into the RABV genome and recombinant virus LBNSE-Flagellin was rescued. To compare the immunogenicity of LBNSE-Flagellin with recombinant virus expressing GMCSF (LBNSE-GMCSF), mice were immunized with each of these rRABVs by intramuscular (i.m.) or oral route. The parent virus (LBNSE) without expression of any foreign molecules was included for comparison. The i.m.-immunized mice were bled at three weeks after the immunization for the measurement of virus neutralizing antibody (VNA) and then challenged with 50 LD50 challenge virus standard (CVS-24). Orally immunized mice were boosted after three weeks and then bled and challenged one week after the booster immunization. It was found that both LBNSE-GMCSF and LBNSE-Flagellin recruited/activated more DCs and B cells in the periphery, stimulated higher levels of adaptive immune responses (VNA), and protected more mice against challenge infection than the parent virus LBNSE in both the i.m. and the orally immunized groups. Together, these studies suggest that recombinant RABV expressing GM-CSF or flagellin are more immunogenic than the parent virus in both i.m. and oral immunizations.
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