Optimization of storage conditions for Puumala virus based vaccine
- Authors: Vetrova A.N.1,2, Kurashova S.S.1, Teodorovich R.D.1, Popova Y.V.1, Blinova E.A.3, Nabatnikov P.A.1, Tkachenko E.А.1, Dzagurova T.K.1
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Affiliations:
- Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
- Sechenov First Moscow State Medical University (Sechenov University)
- Central Research Institute of Epidemiology of The Federal Service on Customers’ Rights Protection and Human Well-being Surveillance
- Issue: Vol 13, No 2 (2023)
- Pages: 376-382
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/2220-7619/article/view/147835
- DOI: https://doi.org/10.15789/2220-7619-OOS-2116
- ID: 147835
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Abstract
We report the effects of storage conditions and human serum albumin addition to the vaccine composition on the immunogenic properties of an experimental vaccine against hemorrhagic fever with renal syndrome. To obtain an experimental vaccine, the Puumala virus, propagated in Vero cells culture, was concentrated, inactivated with beta-propiolactone, and purified by chromatography on the Capto™Core 700 multimodal sorbent (GE Healthcare). The target component in the vaccine was 2±0.2 × 106 of viral RNA copies/ml. The humoral immune response to the vaccine was determined by measuring the neutralizing antibodies in the blood serum of immunized Syrian hamsters (Mesocricetus auratus). It was revealed that the Puumala virus inactivated with beta-propiolactone induces a pronounced humoral immune response, which indicates preservation of relevant immunogenic epitopes. Аccording to our study, viral RNA is more stable during storage of the inactivated vs. intact virus. It was confirmed that full virus inactivation occurred after 24 hours of storage at 37°C. A significant decrease in the virus immunogenicity during the thermal inactivation was noted, which confirms the need for careful selection of storage conditions for thermolabile Hantaviruses. A direct correlation was observed between viral titer and viral RNA copy number/ml. Adding human serum albumin stabilized viral infectivity during storage: Puumala virus titer remained at the same level for 3 months of storage at 6±2°C, whereas without albumin, the titer decreased to undetectable level. The addition of 0.1% human serum albumin to the inactivated virus stabilized its immunogenic properties during long-term storage. It was shown that vaccine preparations with human serum albumin (0.1–1%) show higher dose-dependent stability upon repeated freezing assessed by detecting viral RNA level and their immunogenicity. It can be assumed that human serum albumin provides better preservation of of viral genetic material during storage, as well the protein epitopes responsible for the protective immune response in the form of neutralizing antibodies induction, undergo less pronounced conformational changes in the presence of albumin. These data support the addition of human serum albumin to the vaccine formulation.
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##article.viewOnOriginalSite##About the authors
Anna N. Vetrova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences; Sechenov First Moscow State Medical University (Sechenov University)
Author for correspondence.
Email: ann.vetr.99@mail.ru
Research Laboratory Assistant, Laboratory of Hemorrhagic Fevers; Magistracy Student of Biotechnology
Russian Federation, Moscow; MoscowSvetlana S. Kurashova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
PhD (Medicine), Leading Researcher, Laboratory of Hemorrhagic Fevers
Russian Federation, MoscowRostislav D. Teodorovich
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
Researcher, Laboratory of Hemorrhagic Fevers
Russian Federation, MoscowYulia V. Popova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
Researcher, Laboratory of Hemorrhagic Fevers
Russian Federation, MoscowEkaterina A. Blinova
Central Research Institute of Epidemiology of The Federal Service on Customers’ Rights Protection and Human Well-being Surveillance
Email: ann.vetr.99@mail.ru
Junior Researcher, Science Team for Genetic Engineering and Biotechnology
Russian Federation, MoscowPavel A. Nabatnikov
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
Leading Technologist
Russian Federation, MoscowEvgeny А. Tkachenko
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
DSc (Medicine), Professor, Scientific Supervisor
Russian Federation, MoscowTamara K. Dzagurova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences
Email: ann.vetr.99@mail.ru
DSc (Medicine), Head of the Laboratory of Hemorrhagic Fevers
Russian Federation, MoscowReferences
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