The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host.
The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host.
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DOI：
10.1016/j.antiviral.2018.04.015
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发表时间：
2018-06
影响因子：
7.6
通讯作者：
Castillo-Olivares J
中科院分区：
文献类型：
--
作者：
Calvo-Pinilla E;Gubbins S;Mertens P;Ortego J;Castillo-Olivares J
非洲马病(AHS)是由非洲马病病毒(AHSV)引起的一种由库蚊叮咬蚊虫传播的致死性马病。AHS是撒哈拉以南非洲的地方性疾病，但该区域以外的地区也定期记录到毁灭性的疫情。随着与AHSV密切相关的蓝舌病毒在反刍动物中引起的频繁流行，在欧洲发生AHS暴发的已知风险增加了。出于生物安全方面的考虑，AHS减毒疫苗被认为不适合在非流行国家使用。此外，弱毒疫苗和灭活疫苗与DIVA(区分感染动物和接种疫苗的动物)策略不兼容。所有这些因素刺激了更安全、更有效和与DIVA相容的新型AHS疫苗的发展。我们之前在小鼠模型和马身上证明了编码AHSV外衣壳蛋白(AHSV-VP2)的重组改良痘苗病毒(MVA)疫苗可以诱导病毒中和抗体(VNAb)并对AHSV产生保护作用。被动免疫研究表明，MVA-VP2诱导的免疫与疫苗免疫前的VNAb滴度有关。对这些MVA-VP2实验疫苗的接种分析表明，它们含有预先形成的AHSV-VP2。我们继续研究MVA-VP2疫苗中存在的预先形成的AHSV-VP2对MVA-VP2疫苗免疫原性的影响。因此，我们比较了以前接种过以下疫苗的攻击小鼠的免疫相关性：a)MVA-VP2(活的)；b)MVA-VP2(活的和蔗糖梯度纯化的)；c)MVA-VP2(紫外线灭活)；d)MVA-VP2(紫外线灭活和稀释)；e)MVA-VP2(热灭活)；f)MVA-VP2(紫外线灭活)；C)MVA-VP2(纯化)；以及h)野生型MVA-VP2(未插入)。这些实验的结果表明，MVA-VP2(活)疫苗的保护作用最强，所有其他疫苗的保护作用与疫苗接种中预先形成的AHSV-VP2水平密切相关。表达非洲马瘟病毒VP2的MVA-VP2疫苗在小鼠模型和马体内诱导保护性免疫。实验性的MVA-VP2疫苗如果没有经过蔗糖梯度纯化，则在接种物中含有预制的AHSV-VP2。MVA-VP2疫苗在感染MVA-VP2的细胞中表达AHSV-VP2。在MVA-VP2疫苗中预先形成的AHSV-VP2和重新合成的AHSV-VP2均有助于MVA-VP2的免疫原性。
African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV. Attenuated vaccines for AHS are considered unsuitable for use in non-endemic countries due bio-safety concerns. Further, attenuated and inactivated vaccines are not compatible with DIVA (differentiate infected from vaccinated animals) strategies. All these factors stimulated the development of novel AHS vaccines that are safer, more efficacious and DIVA compatible. We showed previously that recombinant modified Vaccinia Ankara virus (MVA) vaccines encoding the outer capsid protein of AHSV (AHSV-VP2) induced virus neutralising antibodies (VNAb) and protection against AHSV in a mouse model and also in the horse. Passive immunisation studies demonstrated that immunity induced by MVA-VP2 was associated with pre-challenge VNAb titres in the vaccinates. Analyses of the inoculum of these MVA-VP2 experimental vaccines showed that they contained pre-formed AHSV-VP2. We continued studying the influence of pre-formed AHSV-VP2, present in the inoculum of MVA-VP2 vaccines, in the immunogenicity of MVA-VP2 vaccines. Thus, we compared correlates of immunity in challenged mice that were previously vaccinated with: a) MVA-VP2 (live); b) MVA-VP2 (live and sucrose gradient purified); c) MVA-VP2 (UV light inactivated); d) MVA-VP2 (UV light inactivated and diluted); e) MVA-VP2 (heat inactivated); f) MVA-VP2 (UV inactivated) + MVA-VP2 (purified); g) MVA-VP2 (heat inactivated) + MVA-VP2 (purified); and h) wild type-MVA (no insert). The results of these experiments showed that protection was maximal using MVA-VP2 (live) vaccine and that the protection conferred by all other vaccines correlated strongly with the levels of pre-formed AHSV-VP2 in the vaccine inoculum. MVA-VP2 vaccines (expressing African horse sickness virus VP2) induce protective immunity in mouse model and in horses. Experimental MVA-VP2 vaccines contain preformed AHSV-VP2 in the inoculum if they are not sucrose-gradient purified. MVA-VP2 vaccines express AHSV-VP2 in MVA-VP2 infected cells. Both pre-formed AHSV-VP2 and ‘de novo’ synthesised AHSV-VP2 in MVA-VP2 vaccinates contribute to MVA-VP2 immunogenicity.
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影响因子：
5.5
作者：
Alberca, Berta;Bachanek-Bankowska, Katarzyna;Cabana, Marta;Calvo-Pinilla, Eva;Viaplana, Elisenda;Frost, Lorraine;Gubbins, Simon;Urniza, Alicia;Mertens, Peter;Castillo-Olivares, Javier
通讯作者：
Castillo-Olivares, Javier
影响因子：
5.5
作者：
Guthrie, Alan J.;Quan, Melvyn;MacLachlan, N. James
通讯作者：
MacLachlan, N. James
DOI：
10.3390/v6072735
发表时间：
2014-07-17
期刊：
Viruses
影响因子：
--
作者：
Altenburg AF;Kreijtz JH;de Vries RD;Song F;Fux R;Rimmelzwaan GF;Sutter G;Volz A
通讯作者：
Volz A
影响因子：
3.7
作者：
BURRAGE, TG;TREVEJO, R;LAEGREID, WW
通讯作者：
LAEGREID, WW
影响因子：
1.8
作者：
Minke, JM;Fischer, L;Audonnet, JC
通讯作者：
Audonnet, JC