Affiliation:
1. FSBI «Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology» of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
2. FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia
Abstract
Introduction. 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.Material and methods. 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.Results. 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.Discussion. 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.Conclusion. 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».
Publisher
Central Research Institute for Epidemiology
Subject
Infectious Diseases,Virology,General Medicine
Reference19 articles.
1. Castillo-Solórzano C., Reef S.E., Morice A., Vascones N., Chevez A.E., Castalia-Soares R., et al. Rubella vaccination of unknowingly pregnant women during mass campaigns for rubella and congenital rubella syndrome elimination, the Americas 2001–2008. J. Infect. Dis. 2011; 204 (Suppl. 2): S713–7. https://doi.org/10.1093/infdis/jir489.
2. Shamsutdinova O.A. Live attenuated vaccines for the immunoprophylaxis. Infektsiya i immunitet. 2017; 7(2): 107–16. https://doi.org/10.15789/2220-7619-2017-2-107-116 (in Russian).
3. Hofmann J., Kortung M., Pustowoit B., Faber R., Piskazeck U., Liebert U.G. Persistent fetal rubella vaccine virus infection following inadvertent vaccination during early pregnancy. J. Med. Virol. 2000; 61(1): 155–8. https://doi.org/10.1002/(sici)1096-9071(200005)61:1%3C155::aid-jmv25%3E3.0.co;2-o.
4. Da Silva e Sá G.R., Camacho L.A., Stavola M.S., Lemos X.R., Basílio de Oliveira C.A., Siqueira M.M. Pregnancy outcomes following rubella vaccination: A prospective study in the State of Rio de Janeiro, Brazil, 2001–2002. J. Infect. Dis. 2011; 204(2): S722–8. https://doi.org/10.1093/infdis/jir408.
5. Keller-Stanislawski B., Englun J.A., Kang G., Mangtani P., Neuzil K., Nohynek H., et al. Safety of immunization during pregnancy: A review of the evidence of selected inactivated and live attenuated vaccines. Vaccine. 2014; 32(52): 7057–64. https://doi.org/10.1016/j.vaccine.2014.09.052.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献