Title: Lack of immune responses to Mycobacterium tuberculosis DosR regulon proteins 1 following BCG vaccination 2 3

Abstract 2 BCG is widely used as a vaccine against tuberculosis (TB) despite its variable protective 3 efficacy. Relatively little is known about the immune response profiles following BCG 4 vaccination in relation to protection against TB. Here we tested whether BCG vaccination 5 results in immune responses to DosR (Rv3133c) regulon encoded proteins. These so-called 6 TB latency antigens are targeted by the immune system during persistent Mycobacterium 7 tuberculosis infection and have been associated with immunity against latent M. tuberculosis 8 infection. 9 In silico analysis of the DosR regulon in BCG and M. tuberculosis showed at least 97% 10 homology in amino acid sequence, with 41 out of 48 genes being identical. Transcriptional 11 profiling of 14 different BCG strains, under hypoxia and nitric oxide exposure in vitro, 12 revealed a functional DosR regulon similar to that observed in M. tuberculosis . 13 Next, we assessed human immune responses to a series of immuno-dominant TB latency 14 antigens and found that BCG vaccination