Does intravenous vaccination with self-killing BCG lead to development of an immune response that protects against <i>Mycobacterium tuberculosis</i>?

Abstract The use of intradermal BCG offers limited protection against tuberculosis. Intravenous (IV) administration has shown to produce robust infection in a non-human primate model However, the duration exposure and time required elicit an efficacious, protective response is unknown safety IV live remains concern. Here we investigated whether self-limiting strain (killswitchBCG; ksBCG) could induce responses macaques. ksBCG uses two transcriptionally repressible lysins; inducer doxycycline for repression, with absence leading death. Our first study demonstrated vivo killing once stopped elicited robust, multicellular immune airways lung up 8 weeks, similar standard BCG. In current are assessing conferred Mycobacterium tuberculosis ksBCG. Mauritian cynomolgus macaques (MCM) were vaccinated intravenously 5 months post vaccination, animals challenged M. later euthanized 12 weeks infection. Bronchoalveolar lavages routinely taken throughout study, alongside tissue samples, analyzed using spectral flow cytometry. presence multiple cell types (CD4, CD8, gd T cells, B NK cells), cytokines (IFNg, IL-2, IL-17, TNF) cytotoxic molecules (granzymes K, perforin, granulysin), as well bacterial burden will be assessed determine level provided by NIH R01 AI143788