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接种纯化鸡胚细胞狂犬病疫苗(PCECV)诱导的抗体对不同的狂犬病病毒种的交叉中和作用。

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.

机构信息

a Novartis Vaccines; Medical Affairs ; Marburg , Germany.

出版信息

Hum Vaccin Immunother. 2014;10(10):2799-804. doi: 10.4161/21645515.2014.972741.

Abstract

BACKGROUND

Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2.

MATERIAL & METHODS: Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV.

RESULTS

Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate).

CONCLUSION

Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research.

摘要

背景

狂犬病是一种被忽视的人畜共患疾病,由属于 Lyssavirus 属的病毒引起。在亚洲和非洲的流行国家,估计有 6 万人死于狂犬病,其中大多数是由狗传播的经典狂犬病病毒(RABV)引起的。在过去的十年中,已经鉴定出该属中的新物种。与此同时,存在 15 种(提议或分类)物种,包括澳大利亚蝙蝠 Lyssavirus(ABLV)、欧洲蝙蝠 Lyssavirus(EBLV-1 和 -2)、Duvenhage 病毒(DUVV),以及 Lagos 蝙蝠病毒(LBV)和 Mokola 病毒(MOKV),最近还发现了新的物种,如 Bokeloh 蝙蝠 Lyssavirus(BBLV)、Ikoma 蝙蝠 Lyssavirus(IKOV)或 Lleida 蝙蝠 Lyssavirus(LLBV)。这些 Lyssavirus 物种中的大多数存在于蝙蝠宿主中,其中一些已经导致人类感染和死亡。以前的工作表明,纯化鸡胚细胞狂犬病疫苗(PCECV)不仅能诱导针对经典 RABV 的免疫反应,还能诱导针对 ABLV、EBLV-1 和 EBLV-2 的交叉中和抗体。

材料和方法

本研究扩展使用与我们之前的研究相同的血清样本,使用快速荧光焦点抑制试验(RFFIT)测量血清抗体的交叉中和活性,以检测其他选定的非经典 Lyssavirus 感兴趣的物种,即 DUVV 和 BBLV,以及 MOKV 和 LBV。

结果

接种 PCECV 后产生的抗体对 BBLV 和 DUVV 的中和能力与对 ABLV 和 EBLV-1 和 -2 的中和能力相同。正如预期的那样,对于系统发育上更远的 LBV 物种,没有发现交叉中和活性。有趣的是,94 份血清样本中有 15 份(16%)对 RABV 的中和抗体滴度呈阳性,对一种特定的 MOKV 株(埃塞俄比亚分离株)表现出特异性的交叉中和活性(比 RABV 低 65 倍),而对另一种不同的株(尼日利亚分离株)则没有。

结论

交叉中和活性部分与病毒种的系统发育距离相关。证明了与 phylogroup 1 的 BBLV 和 DUVV 物种的交叉中和活性,与之前对 ABLV 和 EBLV-1 和 -2 的交叉中和活性的结果一致。需要进一步研究针对更遥远的 Lyssavirus 物种(如选定的 MOKV 株)的潜在部分交叉中和活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322e/5443070/44509cf70e84/khvi-10-10-972741-g001.jpg

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