Immunological Markers that Correlate with Protection Immunity Against Tularemia Infection

Abstract

An efficient immune response to tularemia is dependent on a strong cell-mediated component. We tried to identify markers of cellular immune responses that indicate a vaccine efficacy against tularemia. BALB/c mice were immunized with mutant F. tularensis 15∆23A and/or F. tularensis 15 NIIEG strains and then were challenged i.n. with F. tularensis Schu. We compared the influence of F. tularensis antigens (tularinum) in vitro on production of IL-1, IL-5, IL-6, IL-17, IFN-γ, and TNF-α by splenocytes obtained from intact mice and mice immunized with mutant F. tularensis 15∆23A and/or F. tularensis 15 NIIEG strains. We also compared expression of CD28, CD154, TLR-2, and CD69 markers on CD4 and CD8 T-cells after activation with tularinum in vitro. We found that tularinum-induced CD4(+) T-cells increased TNF-α and IFN-γ synthesis and expression of CD69 only in group mice with high degree of post immunization protection against F. tularensis Schu challenge. Estimation of CD69 expression on CD3(+)CD4(+) cells and IFN-γ, TNF-α synthesis by CD4(+) T-lymphocytes could be useful for determination protect ability of antitularemia immunity.

Differential In Vitro Cultivation of Francisella tularensis Influences Live Vaccine Protective Efficacy by Altering the Immune Response

“…Splenocytes derived from the BHIM- Ft sodB -immune mice also produced more IFN-γ, IL-12p40, IL-17A, and IL-6 during BMDMs-splenocyte co-culture. This also supports prior studies suggesting that increased production of IFN-γ, IL-12p40, IL-17A, and IL-6 may serve as biomarkers for identifying more efficacious vaccine strategies against Ft ( 31 , 33 , 43 ).…”

Development of a Monoclonal Antibody to Pig CD69 Reveals Early Activation of T Cells in Pig after PRRSV and ASFV Infection

“…Therefore, the detection of CD69 is a reliable indicator for the early activation of T cells. The activation state of immune cells after infection or immunization was routinely determined by detecting CD69 expression, along with other markers in human and mouse models [5,6,[8][9][10][11]. For instance, by detecting CD69 expression, mycobacterium tuberculosis-specific CD4 T cells were shown to be activated in the mediastinal lymph node as early as on day 9 after infection [12] and tissue-resident memory CD8 T cells significantly increased in the skin in a model of vaccinia virus skin infection [13].…”

“…For instance, by detecting CD69 expression, mycobacterium tuberculosis-specific CD4 T cells were shown to be activated in the mediastinal lymph node as early as on day 9 after infection [12] and tissue-resident memory CD8 T cells significantly increased in the skin in a model of vaccinia virus skin infection [13]. In addition, CD69 expression on CD4 T-cellT cells was found to be correlated with immune protection against tularemia [11]. However, these strategies have not yet been validated and applied in pigs, due to the lack of a specific antibody to pig CD69, hindering the evaluation of the early activation of cellular immunity in pigs during infection or immunization.…”

Perspectives approach to the assessment of the quality of the vaccine plague live in terms of immunogenicity. Epidemiology and Vaccinal Prevention

“…По данным современной литературы, диагностически информативным показателем клеточной антигенреактивности на ранних сроках после иммунизации может выступать маркер активации лимфоцитов CD25 -высокоаффинный рецептор интерлейкина 2 (IL-2Ra), экспрессирующийся активированными Т-лимфоцитами. Проведенные ранее исследования указывают на возможность и перспективу использования антигенспецифических клеточных тестов in vitro для оценки формирования поствакцинального противочумного иммунитета в ранние сроки после иммунизации [7][8][9].…”