Choice of Vaccination Regimen against Orthopoxvirus Infections in a Mouse Model
摘要
The purpose of this study is to evaluate the effect of dose and frequency of immunization of BALB/c mice with intradermal (ID) injection of the LIVP strain of vaccinia virus (VACV) on the level of their protection against the ectromelia virus (ECTV), which is highly virulent for mice. Immunization of mice was carried out using a single or double ID injection of VACV LIVP with an interval of 28 days at a dose of 105 plaque-forming units (PFU), as well as a single injection at a dose of 106 PFU. In blood sera taken from mice during their lifetime, the dynamics of biosynthesis of VACV-specific IgG was determined with enzyme-linked immunosorbent assay (ELISA) up to 140 days postvaccination (dpv). At 142 dpv, groups immunized with the LIVP virus and control animals were intranasally infected with a lethal dose of ECTV and the indicators of clinical manifestations of infection, body weight of animals, and their death were monitored. At 28 dpv the level of antibodies in mice vaccinated with VACV LIVP at a dose of 106 PFU significantly exceeded this level in mice vaccinated with the same virus at a dose of 105 PFU. Repeated immunization with VACV LIVP at a dose of 105 PFU on 28 dpv led to a significant increase in the biosynthesis of virus-specific IgG and the level of analyzed antibodies in this group of mice corresponded to a similar indicator for the group of mice vaccinated once with VACV LIVP at a dose of 106 PFU. After infection with a lethal dose of ECTV, all animals in the control group (unvaccinated) died by the eighth day after infection, while those vaccinated with VACV LIVP once at a dose of 105 PFU died by the 14th day. In groups of mice vaccinated twice at a dose of 105 PFU and once at a dose of 106 PFU, 80% of the subjects survived. To maintain a long-term protective immune response to vaccination with live VACV, a high dose of this virus must be used. Alternatively, a lower vaccination dose can be used, but in this case, revaccination should be carried out.