Identifying correlates of protection from <i>Yersinia pestis</i> on a mouse model and assessing an opportunity for their use as markers of human vaccination efficiency

Abstract

In case no assessment of changes in incidence rate can be used as an indicator for effectiveness of applied live plague vaccine, it is really necessary to search for other, particularly immunological correlates for vaccine-based protection. The aim of this study was to reveal immunological correlates for plague protection in mice immunized with Yersinia pestis EV NIIEG, and assess dynamics changes in select markers of plague vaccinated subjects. BALB/c mice were immunized with Y. pestis EV at dose of 2 102, 1 103, 5 103, 2.5 104 CFU, and on day 21 they were challenged with Y. pestis 231 at a dose of 400 LD50. Immunogenicity was calculated by the Kerber method and ImD50 was determined. Volunteers 20 subjects who were first vaccinated with live plague vaccine and 20 subjects who were not vaccinated against the plague. Blood cytokine production was measured on the LAZURIT analyzer (Dynex Technologies, USA) in mouse groups before Y. pestis 231 infection on day 14 as well as 21 days after vaccination, in humans before vaccination, 1, 6 and 12 months after vaccination. The immunized mice showed a significant increase (by 2.2 times) in the induced production of IFN and a moderate increase in the concentration of TNF, IL-10 and IL-17A on day 14 of disease. A high correlation was found between the survival rate of animals and the level of antigen-/mitogen-induced IFN production (r = 0.94, p = 0.039), both on day 14 and 21, as well as a noticeable relationship with the level of produced IL-10 and IL-17A on day 14. One month after vaccination volunteers had significantly increase by month 6 (p 0.05) levels of IFN, TNF, IL-10, IL-17A, although only for IFN and IL-17A, the persistence of induced production was noted at a fairly high level for up to a year. Thus, IFN and IL-17A can be considered as possible informative correlates of mouse protection against Y. pestis on days 14 and 21, considering the increase in the induced production of these cytokines as adequate markers of the protective efficacy of immunization, and assessing dynamics in these parameters of volunteers vaccinated with the plague live vaccine, the increase in the levels of IFN and IL-17A can be considered as a favorable prognostic marker of the immunological efficacy of the vaccine in the period from the month 6 to 12 of observation.