Abstract
Vaccine development for tuberculosis is a global priority. Our studies using Collaborative Cross (CC) mice show that genetic diversity influences the efficacy of BCG, the most widely used TB vaccine. BCG vaccination of CC042 mice reduced their lung bacillary burden and increased their survival following low-dose aerosol Mycobacterium tuberculosis infection (MTBI), despite impaired T cell trafficking due to a defective Itgal gene. BCG vaccination conferred early bacillary control which appeared to be independent of B cell or T cell recall responses following MTBI. In contrast, long term survival of BCG-vaccinated CC042 mice after MTBI required T cells. Thus, CC042 mice reveal two phases of immunity induced by BCG: an early phase mediated by innate immunity or innate-like T cells and a later phase mediated by conventional memory CD4 and/or CD8 T cells. Although measurement of vaccine-induced protection 30 days after MTBI is a standard measure of vaccine efficacy in the TB model, this time point might be independent of memory T cells in CC042 mice. Our results suggest that vaccine-elicited innate/innate-like responses could have a larger role in protection than previously considered. The concordance between lung CFU, pathology, and survival make CC042 mice useful for mechanistic studies on vaccine-induced immunity.
Authors
Abiola F. Ogunsola, Rocky Lai, Kelly Cavallo, Anthony V. Tran, Gillian L. Beamer, Samuel M. Behar
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
