Immune modulating effect by a phosphoprotein-deleted rabies virus vaccine vector expressing two copies of the rabies virus glycoprotein gene.
Immune modulating effect by a phosphoprotein-deleted rabies virus vaccine vector expressing two copies of the rabies virus glycoprotein gene.
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DOI：
10.1016/j.vaccine.2008.08.069
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发表时间：
2008-11-25
期刊：
影响因子：
5.5
通讯作者：
McGettigan JP
中科院分区：
文献类型：
--
作者：
Cenna J;Tan GS;Papaneri AB;Dietzschold B;Schnell MJ;McGettigan JP
疫苗引起的免疫反应类型是决定其预防感染或疾病有效性的关键因素。狂犬病毒（RV）灭活疫苗株和活疫苗株分别引起IgG1偏向和IgG1/ igg2a平衡的抗体反应。然而，IgG2a抗体是抗病毒效应功能的有效诱导剂，因此，能够引发IgG2a偏向抗体反应的病毒疫苗载体可能对RV感染更有效。在这里，我们描述了活的复制缺陷磷蛋白(P)缺失的RV载体（SPBN-ΔP）或表达两个拷贝RV糖蛋白(G)基因的重组P缺失病毒（SPBN-ΔP-RVG）的体液免疫反应，并将其与紫外线灭活的RV进行比较。接种uv灭活RV的小鼠主要诱导IgG1特异性抗体反应，而活的重组SPBN-ΔP则表现出IgG1/IgG2a混合抗体反应，这与复制能力强的亲本病毒的同型谱一致。致病性RV攻击后小鼠的存活率表明，与紫外线灭活SPBN-ΔP相比，活SPBN-ΔP的效率高10倍。此外，SPBN-ΔP-RVG诱导的IgG2a反应比SPBN-ΔP更快速、更强，能更有效地保护小鼠。值得注意的是，103 ffu SPBN-ΔP-RVG诱导抗RV抗体，对小鼠致病性RV攻击具有100%的保护作用。增强的免疫反应不仅针对RVG，还针对核糖核蛋白（RNP），这表明SPBN-ΔP-RVG中两个RVG基因的表达也增强了对其他RV抗原的免疫反应。此外，肌肉注射105 ffu/小鼠SPBN-ΔP的Rag2小鼠未出现狂犬病临床症状，脊髓和脑内未检测到病毒RNA。因此，p缺失载体的安全性以及SPBN-ΔP-RVG诱导igg2a免疫反应的发生和强度表明，该载体作为RV或其他传染病的治疗性或预防性疫苗具有很大的前景。
The type of immune response induced by a vaccine is a critical factor that determines its effectiveness in preventing infection or disease. Inactivated and live rabies virus (RV) vaccine strains elicit an IgG1-biased and IgG1/IgG2a-balanced antibody response, respectively. However, IgG2a antibodies are potent inducers of anti-viral effector functions, and therefore, a viral vaccine vector that can elicit an IgG2a-biased antibody response may be more effective against RV infection. Here we describe the humoral immune response of a live replication-deficient phosphoprotein (P)-deleted RV vector (SPBN-ΔP), or a recombinant P-deleted virus that expresses two copies of the RV glycoprotein (G) gene (SPBN-ΔP-RVG), and compare it to a UV-inactivated RV. Mice inoculated with UV-inactivated RV induced predominantly an IgG1-specific antibody response, while live recombinant SPBN-ΔP exhibited a mixed IgG1/IgG2a antibody response, which is consistent with the isotype profiles from the replication-competent parental viruses. Survivorship in mice after pathogenic RV challenge indicates a ten-fold higher efficiency of live SPBN-ΔP compared to UV-inactivated SPBN-ΔP. In addition, SPBN-ΔP-RVG induced a more rapid and robust IgG2a response that protected mice more effectively than SPBN-ΔP. Of note, 103 ffu of SPBN-ΔP-RVG induced anti-RV antibodies that were 100% protective in mice against pathogenic RV challenge. The increased immune response was directed not only against RV G but also against the ribonucleoprotein (RNP), indicating that the expression of two RV G genes from SPBN-ΔP-RVG enhances the immune response to other RV antigens as well. In addition, Rag2 mice inoculated intramuscularly with 105 ffu/mouse of SPBN-ΔP showed no clinical signs of rabies, and no viral RNA was detected in the spinal cord or brain of inoculated mice. Therefore, the safety of the P-deleted vectors along with the onset and magnitude of the IgG2a-induced immune response by SPBN-ΔP-RVG indicate that this vector holds great promise as either a therapeutic or preventative vaccine against RV or other infectious diseases.
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影响因子：
3.3
作者：
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通讯作者：
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作者：
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