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JMBS 2019, 4(5): 9–16
https://doi.org/10.26693/jmbs04.05.009
Medicine. Reviews

Trained Innate Immunity as the Basis for New Strategies in Vaccine Development

Yelyseyeva I. V., Babych Ye. M., Zhdamarova L. A., Belozersky V. I., Kolpak S. A.
Abstract

The review article deals with new possibilities of rational design of vaccines. Such possibilities are opened by improving knowledge about pathogen-host interactions and mechanisms of the immune system. During the last decade, numerous studies have led to a revision of the paradigm in immunology. It turns out that innate immune cells can create immunological memory similar to that observed in adaptive immunity and appropriate mechanisms for the protection of lower organisms (including archeae, bacteria, invertebrates and plants), which increases their resistance to reinfection. The phenomenon of increasing the resistance of the innate immune system to re-infection was called trained immunity or innate immune memory. A similar enhancement of the function of innate immunity is also described for vertebrates, mammals, and humans. The basis of the trained immunity is the functional reprogramming of the innate immune cells by pattern recognition receptors activating, which results in enhanced non-specific antimicrobial responses when re-encountered with the microbes. During the induction of trained immunity, due encounters with inflammatory stimuli, the cells undergo functional and transcriptional reprogramming toward increased activation and development of altered responses to subsequent stimuli. Trained immunity can be induced by various infectious or non-infectious agents, namely: LPS, β-glucan, chitin, oxidized low-density lipoprotein (oxLDL)), as well as viruses or even parasites are considered as potent inducers of innate immune memory. Innate immune cells (monocytes, macrophages, dendritic cells, NK cells) can provide protection against some infections in vaccination models regardless of lymphocytes. The literature describes nonspecific protective effects of BCG, measles vaccine, oral polio vaccine, and experimental vaccines, such as the live attenuated goiter's BPZE1 vaccine, the oral live attenuated Salmonella Typhi Ty21a vaccine, and other ones, the effect of which is associated with trained immunity. Many facts of cross-protection between infections with different pathogens have been accumulated. Experimental studies have shown that priming mice with microbial ligands of pattern recognition receptors can protect against subsequent lethal infection. The data of growing body of research suggest that epigenetic reprogramming underlies innate immune tolerance. Trained immunity can also play a significant role in supporting various disorders: induction and / or maintenance of autoimmune and auto-infectious diseases, appearance of various harmful processes that are associated with the development of atherosclerosis, diabetes, neurodegenerative diseases. Since trained immunity is important for protecting of the human body and responses to the vaccine, trained immunity modulation is a promising direction for new vaccine approaches, therapies and therapeutic goals like: potentiation of trained immunity can protect against secondary infections and invasive immunotolerant states, and treatment of immunodeficiencies. The possibility of using of the force of the adaptive potential of lymphoid and myeloid cell-mediated innate immunity should be considered in the development of next-generation vaccine adjuvants.

Keywords: innate immunity, immunological memory, development of vaccines

Full text: PDF (Ukr) 261K

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