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狂犬病疫苗对犬猫的效力及在小鼠模型中对欧洲2型蝙蝠狂犬病病毒的防护作用

Efficacy of rabies vaccines in dogs and cats and protection in a mouse model against European bat lyssavirus type 2.

作者信息

Nokireki Tiina, Jakava-Viljanen Miia, Virtala Anna-Maija, Sihvonen Liisa

机构信息

Finnish Food Safety Authority Evira, Mustialankatu 3, 00790, Helsinki, Finland.

Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, 00014, Helsinki, Finland.

出版信息

Acta Vet Scand. 2017 Oct 2;59(1):64. doi: 10.1186/s13028-017-0332-x.

Abstract

BACKGROUND

Rabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. The success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. Vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. The aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) and cats (n = 722), as well as to investigate the factors influencing the response to vaccination when animals failed to reach a rabies antibody titre of ≥ 0.5 IU/ml. Another aim was to assess the level of protection afforded by a commercial veterinary rabies vaccine against intracerebral challenge in mice with European bat lyssavirus type 2 (EBLV-2) and classical rabies virus (RABV), and to compare this with the protection offered by a vaccine for humans.

RESULTS

A significantly higher proportion of dogs (10.7%, 95% confidence interval CI 10.1-11.3) than cats (3.5%; 95% CI 2.3-5.0) had a vaccination antibody titre of < 0.5 IU/ml. In dogs, vaccination with certain vaccines, vaccination over 6 months prior the time of antibody determination and vaccination of dogs with a size of > 60 cm or larger resulted in a higher risk of failing to reach an antibody level of at least 0.5 IU/ml. When challenged with EBLV-2 and RABV, 80 and 100% of mice vaccinated with the veterinary rabies vaccine survived, respectively. When mice were vaccinated with the human rabies vaccine and challenged with EBLV-2, 75-80% survived, depending on the booster. All vaccinated mice developed sufficient to high titres of virus-neutralising antibodies (VNA) against RABV 21-22 days post-vaccination, ranging from 0.5 to 128 IU/ml. However, there was significant difference between antibody titres after vaccinating once in comparison to vaccinating twice (P < 0.05).

CONCLUSIONS

There was a significant difference between dogs and cats in their ability to reach a post vaccination antibody titre of ≥ 0.5 IU/ml. Mice vaccinated with RABV-based rabies vaccines were partly cross-protected against EBLV-2, but there was no clear correlation between VNA titres and cross-protection against EBLV-2. Measurement of the RABV VNA titre can only be seen as a partial tool to estimate the cross-protection against other lyssaviruses. Booster vaccination is recommended for dogs and cats if exposed to infected bats.

摘要

背景

狂犬病可通过暴露前和/或暴露后预防来预防,包括一系列狂犬病疫苗接种,某些情况下还需使用免疫球蛋白。疫苗接种的成功率可通过测量病毒中和抗体或通过攻毒实验来评估。基于狂犬病病毒的疫苗可对其他与狂犬病病毒密切相关的狂犬病病毒提供交叉保护。目的是评估通过犬(n = 10,071)和猫(n = 722)的抗体反应来衡量的狂犬病疫苗接种成功率,并调查动物未达到狂犬病抗体滴度≥0.5 IU/ml时影响疫苗接种反应的因素。另一个目的是评估一种商业兽用狂犬病疫苗对欧洲蝙蝠狂犬病病毒2型(EBLV - 2)和经典狂犬病病毒(RABV)脑内攻毒的小鼠的保护水平,并将其与人类疫苗提供的保护进行比较。

结果

疫苗接种抗体滴度<0.5 IU/ml的犬(10.7%,95%置信区间CI 10.1 - 11.3)比例显著高于猫(3.5%;95%CI 2.3 - 5.0)。在犬中,接种某些疫苗、在抗体测定时间前6个月以上进行疫苗接种以及体重>60 cm或更大的犬进行疫苗接种,导致未达到至少0.5 IU/ml抗体水平的风险更高。用EBLV - 2和RABV攻毒时,接种兽用狂犬病疫苗的小鼠分别有80%和100%存活。用人类狂犬病疫苗接种小鼠并以EBLV - 2攻毒时,根据加强免疫情况,75 - 80%存活。所有接种疫苗的小鼠在接种后21 - 22天产生了足以抵抗RABV的高滴度病毒中和抗体(VNA),范围为0.5至128 IU/ml。然而,单次接种与两次接种后的抗体滴度之间存在显著差异(P < 0.05)。

结论

犬和猫在达到疫苗接种后抗体滴度≥0.5 IU/ml的能力上存在显著差异。接种基于RABV的狂犬病疫苗的小鼠对EBLV - 2有部分交叉保护,但VNA滴度与对EBLV - 2的交叉保护之间没有明确的相关性。RABV VNA滴度的测量只能被视为评估对其他狂犬病病毒交叉保护的部分工具。如果犬和猫暴露于感染的蝙蝠,建议进行加强免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba8/5625686/961250b4ced1/13028_2017_332_Fig1_HTML.jpg

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