©Copyright 2020 Mayo Foundation for Medical Education and Research 3 protein. STING controls the innate, type I IFN response to double-stranded DNA and cyclic dinucleotides. Individuals with the H232 variant of STING have a much weaker innate immune response to vaccinia virus. Our data help resolve ongoing controversies regarding the role of genetic variants in STING function. Because STING plays an important role in our immune response to DNA viruses and bacteria, our results can be used to predict who will and will not respond to vaccines and treatments, and to design more effective vaccine candidates. Given the role of the STING protein in innate responses to DNA viruses and bacterial pathogens, these data may also be useful in developing novel treatment options for multiple infectious diseases.results. She assisted in drafting the manuscript, revised it for intellectual content and approved the final version.EAV contributed to the study design, participated in data acquisition and interpretation of study results. She assisted in drafting the manuscript, revised it for intellectual content and approved the final version.BRL contributed data analysis and interpretation. She assisted in drafting the manuscript, revised it for intellectual content and approved the final version.DJS supervised and contributed to the data analysis and interpretation. He participated in drafting and revising the manuscript, and approved the final version.MTZ contributed to the interpretation of study results, molecular modeling, data analysis, drafting the manuscript, critical review, and approved the final version.ALO contributed to the design of the study, participated in data analysis and interpretation, assisted in drafting the manuscript, revised the manuscript for intellectual content, and approved the final version.