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- Title
OX40 Ligand Fusion Protein Delivered Simultaneously With the BCG Vaccine Provides Superior Protection Against Murine Mycobacterium tuberculosis Infection.
- Authors
Snelgrove, Robert J.; Cornere, Megan M.; Edwards, Lorna; Dagg, Belinda; Keeble, James; Rodgers, Angela; Lyonga, Daphne E.; Stewart, Graham R.; Young, Douglas B.; Walker, Barry; Hussell, Tracy
- Abstract
Mycobacterium tuberculosis infection claims approximately 2 million lives per year, and improved efficacy of the BCG vaccine remains a World Health Organization priority. Successful vaccination against M. tuberculosis requires the induction andmaintenance of T cells. Targetingmolecules that promote T-cell survivalmay therefore provide an alternative strategy to classic adjuvants. We show that the interaction between T-cell-expressed OX40 and OX40L on antigen-presenting cells is critical for effective immunity to BCG. However, because OX40L is lost rapidly from antigen-presenting cells following BCG vaccination, maintenance of OX40-expressing vaccineactivated T cells may not be optimal. Delivering an OX40L:Ig fusion protein simultaneously with BCG provided superior immunity to intravenous and aerosol M. tuberculosis challenge even 6months after vaccination, an effect that depends on natural killer 1.1+ cells. Attenuated vaccines may therefore lack sufficient innate stimulation to maintain vaccine-specific T cells, which can be replaced by reagents binding inducible T-cell costimulators.
- Subjects
LIGANDS (Biochemistry); BCG vaccines; MYCOBACTERIUM tuberculosis; WORLD Health Organization; T cells; GENE expression; ANTIGEN presenting cells
- Publication
Journal of Infectious Diseases, 2012, Vol 205, Issue 6, p975
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jir868