Identification of Immunological Correlates of Protection during Development of Specific Immunity to Francisella tularensis

Abstract

Live tularemia vaccine is one of the most effective bacterial vaccines. However, it also has high residual virulence for laboratory animals and may cause adverse reactions in individuals with compromised immune systems. The development of a safe and effective tularemia vaccine is impeded by insufficient understanding of the protection correlates. The aim of this work is to review the literature on the development of post-vaccinal immune responses to live tularemia vaccines and recombinant vaccine candidate strains and to determine the immunological correlates of protection in the formation of specific immunity to Francisella tularensis. This review describes the main aspects of the development of innate and adaptive immune responses to the administration of live tularemia vaccines based on attenuated strains of F. tularensis 15 NIIEG and F. tularensis LVS in humans and in experimental tularemia infection in a mouse model. Studying the mechanisms of adaptive immunity and identifying immunological correlates of protection in experimental tularemia in a murine model is crucial for researching new vaccine strains and improving laboratory methods for assessing the T-cell component of immunity. The main focus is on the study of cellular mechanisms underlying the formation of protective immunity in experimental tularemia, the determination of immunological criteria for its evaluation and the role of identified indicators in long-term protection after the end of the active phase of the immune response induced by immunization with vaccines based on attenuated F. tularensis strains. We discuss the effects of vaccination on the differentiation, functional activity, and duration of specific central and effector CD4+ and CD8+ memory T-cells circulation in humans and mice.