Comparison of the Efficacy of Different Schemes for Using Recombinant Vector Vaccines against Ebola Fever, Based on Vaccinia Virus, MVA Strain

L. F. Stovba, O. V. Chukhralya, D. Pavel'ev, N. K. Chernikova, S. Borisevich
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Abstract

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.
使用基于疫苗病毒 MVA 株的重组载体疫苗预防埃博拉热不同方案的效力比较
本综述旨在研究基于疫苗病毒、MVA 染色体和腺病毒载体的疫苗在预防埃博拉病毒病中的应用。对表达丝状病毒科代表抗原决定簇的重组 MVA 株进行了评估,认为它们可能成为疫苗制剂的候选株。将这种病毒用作疫苗载体的条件是,天花没有群体免疫力,而且对健康的成年志愿者、儿童、青少年、肺结核患者、56-80 岁者、确诊的特应性皮炎患者和艾滋病患者安全。此外,以疫苗病毒 MVA 株为基础的疫苗免疫不会引起与心血管疾病相关的并发症。在免疫功能正常和免疫功能低下的小鼠、适应埃博拉病毒的豚鼠、猕猴和眼镜猴身上进行了免疫原性和保护效率的临床前试验。本报告介绍了制作仅表达病毒糖蛋白或病毒糖蛋白和结构蛋白 Vp40 的疫苗的实验结果。鉴于埃博拉热和其他丝状病毒感染的爆发难以预测,因此设计了能够对所有丝状病毒种类提供保护的多价疫苗。同时使用基于重组腺病毒载体和疱疹病毒株的疫苗的临床试验表明,基于重组疱疹病毒株的疫苗具有更明显的安全性。对体液免疫和 T 细胞免疫反应的研究表明,在异源原代/加强免疫方案中,这种载体更适合用于加强免疫。研究还分析了形成强大持久免疫反应的疫苗接种方案。流行病学模型提供的证据表明,与天花根除运动中有效的环状免疫接种相比,预防性免疫接种可使流行病高风险地区的健康人群产生长期免疫力,对控制未来的疫情爆发有更大的益处。当保护的持续时间比保护形成的速度更重要时,通过接种初免/加强免疫引起的免疫水平的提高将比加速环状免疫更有优势。
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