FSBI «Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology» of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing.
FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia.
Vopr Virusol. 2021 Jan 7;65(6):357-363. doi: 10.36233/0507-4088-2020-65-6-6.
Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type» virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V» in the experiment on rhesus macaques.
Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4-7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V» strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys' birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th-30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons.
No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus.
The obtained data demonstrated that vaccine strains of the «Orlov-V» rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed.
The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V».
风疹病毒具有明显的致畸特性，可导致胎儿宫内感染广泛而持续。因此，控制“野生型”病毒株固有的致畸性是活减毒风疹疫苗疫苗株临床前研究的必要阶段。本研究的目的是在恒河猴实验中全面研究风疹病毒疫苗株“Orlov-V”的致畸特性。
将妊娠早期（4-7 岁）的风疹病毒血清阴性雌性恒河猴（n=13）用于实验。实验组（n=9）动物肌肉注射“Orlov-V”株制备物进行单次免疫。对照组（n=3）的猴子用含有 Wistar RA27/3 株的商业疫苗免疫。对照组（n=1）的雌性猴子注射风疹疫苗用溶剂。使用临床、免疫、病理形态学和病毒学方法的综合方法研究风疹病毒疫苗株的潜在致畸特性。在猴子出生后 3 个月内进行临床观察。在感染后第 28-30 天，通过 HI 试验测定免疫猴子血清中的抗体滴度。在出生后第一个月内，应用 ELISA 法测定新生儿血清中的 IgM 抗体。通过电泳检测扩增子的 PCR 检测风疹病毒 RNA。
未发现妊娠期间接种疫苗的猴子所生婴儿先天性风疹感染的标志物。结果表明，PCR 可作为一种信息方法，证实风疹病毒疫苗株无致畸性。
获得的数据表明，“Orlov-V”风疹病毒和 Wistar RA27/3 疫苗株已丧失致畸性。讨论了使用替代策略替代经典病理方法评估抗病毒疫苗的特定安全性的可能性，包括临床、免疫、病理和病毒学方法的综合方法。
本研究结果表明，风疹病毒疫苗株“Orlov-V”无致畸性和高免疫原性。
