This Research Topic is the second volume of the “Community Series in Vaccines and approaches that target trained immunity in COVID-19: immunological mechanisms of action and delivery". Please see Volume I here.

Trained immunity, an innate immunity that has memory, represents a paradigm change in immunity. Innate immune cells, such as myeloid cells and natural killer cells, can acquire certain levels of immune “memory” properties in responding to stimulations from bacterial, fungal, viral components, as well as cytokines and Toll-like receptor (TLR) agonists. When the hosts encounter the same or different stimulants for a second time, enhanced or decreased immune mediators are produced to generate one of two opposing types of trained immunity: training and tolerance programs. As this process is achieved through complex epigenetic and metabolic programming of both matured innate cells and immature hematopoietic precursors, the imprinted phenotypes can be maintained for a relatively long period of time.

Innate memory can be incorporated in the design of future vaccines and immunotherapeutic approaches. The nonspecific nature of trained immunity mediates heterologous protection against diseases. For example, BCG decreases the incidence of not only tuberculosis but also several viral infections, possibly including SARS-CoV-2 infections. Several clinical trials are currently underway to determine the role of BCG in preventing COVID-19. The mechanisms of how certain pathogens or vaccines might confer protection against SARS-CoV-2 transmission and/or amelioration of COVID-19 severity have not been determined yet.

The putative roles of trained immunity induced by different stimulants or vaccinations in preventing COVID-19 and other infectious diseases are being investigated. However, high toxicity and off-target adverse effects of the compounds that are available to manipulate trained immunity prevent them from being used widely. The mechanisms of inducing and maintaining specific types of trained immunity are far from being fully understood. Thus, it is important to carry out basic research to characterize the specific trained immunity induced by different stimuli and vaccination, and to identify the specific trained immunity that mediates protection against certain diseases. Other limitations of trained immunity, including intermediate duration and limited local tissue distribution, need to be addressed as well.

This research topic will give a comprehensive overview on innate memory and its roles in preventing COVID-19, with particular emphasis on the molecular mechanisms of specific trained immunity induction, maintenance, and specific therapeutic strategies targeting innate memory. The themes addressed by this Research Topic will include, but are not limited to, the following:

• In vitro and in vivo induction of trained immunity by different stimuli or vaccinations
• Vaccines and therapeutic approaches that utilize or target trained immunity in COVID-19
• Roles and mechanisms of innate memory in preventing COVID-19
• Specific approaches to reduce side effects and increase the specific targeting of innate cells such as natural killer cells, myeloid cells, and their progenitors

We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.

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