Cellular and Epigenetic Aspects of Trained Immunity and Prospects for Creation of Universal Vaccines in the Face of Increasingly Frequent Pandemics

The inevitability of pandemics creates an urgent requirement for emergency action to develop effective technologies to reduce harm to the human population in the period between the onset of an epidemic and the development and production of a vaccine. In this review we discuss the possibility of engineering universal vaccines. Such vaccines would exploit the nonspecific potential of innate immunity, would allow the population to be vaccinated when an unidentified pathogen appears, and would reduce disease severity until pathogen-specific vaccines become available. There are strong evidences that bacterial or viral vaccines such as BCG, measles and polio have heterologous protective effects against unrelated pathogens. This is attributed to the innate immune system’s ability to maintain the memory of past infections and use it to develop immune defenses against new ones. This effect has been called “trained” immunity. The use of trained immunity may also represent an important new approach to improving existing vaccines or to developing new vaccines that combine the induction of classical adaptive immune memory and innate immune memory. Such approaches can be boosted by genetic technology and prove extremely useful against future pandemics.