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灭活西尼罗河病毒(WNV)疫苗 Duvaxyn WNV 可预防小鼠感染高度神经侵袭性的 2 型 WNV 株。

Inactivated West Nile Virus (WNV) vaccine, Duvaxyn WNV, protects against a highly neuroinvasive lineage 2 WNV strain in mice.

机构信息

Zoonosis Research Unit, Department Medical Virology, Room 2.72, Pathology Building, Prinshof Campus, 5 Bophela Road, University of Pretoria, South Africa.

出版信息

Vaccine. 2013 Aug 20;31(37):3856-62. doi: 10.1016/j.vaccine.2013.06.059. Epub 2013 Jun 29.

Abstract

BACKGROUND

Lineage 2 West Nile Virus (WNV) is endemic to southern Africa and Madagascar, and has recently been associated with encephalitis outbreaks in humans and horses in South Africa, central Europe, Italy and Greece. Commercial vaccines have mostly been evaluated against WNV lineage 1 strains and their efficacy against lineage 2 strains rarely reported.

METHODS

To evaluate protection of Duvaxyn WNV vaccine against lineage 2 strains associated with encephalitis in South Africa, mice were vaccinated twice intramuscularly three weeks apart, and challenged four weeks later with highly neuroinvasive lineage 1 strain NY385/99 or lineage 2 strain SPU93/01. Neutralising antibody titres were measured at the time of challenge and three weeks later. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were conducted on brains of mice that succumbed during the trial, on controls and on vaccinated mice that survived.

RESULTS

Serum neutralising antibodies in vaccinated mice were detected but low three weeks after primovaccination. Three weeks post-challenge, vaccinated mice had significantly higher serum neutralising antibody titres against both lineages than unvaccinated controls. After challenge, all vaccinated mice remained healthy but all unvaccinated mice demonstrated severe neurological signs with 75% mortality rate. WNV was not detected in brains of vaccinated mice whereas virus replicated in most unvaccinated mice challenged with either lineage. Gross and microscopic lesions were found only in unvaccinated mice challenged with both lineages.

CONCLUSION

Duvaxyn WNV vaccine provided complete protection against challenge with lineage 2 WNV and stimulated significant cross protective neutralising antibodies in mice against lineage 2.

摘要

背景

西尼罗河病毒(WNV)谱系 2 在南非和马达加斯加流行,最近与南非、中欧、意大利和希腊的人类和马脑炎爆发有关。商业疫苗主要针对 WNV 谱系 1 株进行了评估,其对谱系 2 株的功效很少有报道。

方法

为了评估 Duvaxyn WNV 疫苗对南非脑炎相关谱系 2 株的保护作用,小鼠肌肉内两次接种,间隔 3 周,4 周后用高度神经侵袭性谱系 1 株 NY385/99 或谱系 2 株 SPU93/01 进行攻毒。在攻毒时和 3 周后测量中和抗体滴度。对试验过程中死亡、对照和存活的疫苗接种小鼠的大脑进行免疫组织化学和逆转录聚合酶链反应(RT-PCR)检测。

结果

疫苗接种小鼠血清中检测到中和抗体,但初次接种后 3 周时抗体水平较低。攻毒后 3 周,疫苗接种小鼠对两种谱系的血清中和抗体滴度均显著高于未接种对照组。攻毒后,所有疫苗接种小鼠均保持健康,但所有未接种小鼠均出现严重神经症状,死亡率为 75%。WNV 未在疫苗接种小鼠的大脑中检测到,而病毒在大多数用两种谱系攻毒的未接种小鼠中复制。仅在接种两种谱系的未接种小鼠中发现大体和显微镜下病变。

结论

Duvaxyn WNV 疫苗对谱系 2 WNV 攻毒提供了完全保护,并在小鼠中刺激了针对谱系 2 的显著交叉保护中和抗体。

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