The
COVID-19 pandemic triggered an unparalleled pursuit of
vaccines to induce specific adaptive immunity, based on virus-
neutralizing antibodies and T cell responses. Although several
vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat
infections. Innate immune responses, triggered by a family of
pattern recognition receptors, induce
interferons and other
cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-
attenuated vaccines (LAV) targeting
tuberculosis,
measles, and
polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other
infectious diseases, including
COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could
complement the development of specific
vaccines, bridging the protection gap until specific
vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific
vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.