OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection.
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| 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 and maintenance of T cells. Targeting molecules that promote T-cell survival may 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 vaccine-activated 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 6 months 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.
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| Authors | Robert J Snelgrove, Megan M Cornere, Lorna Edwards, Belinda Dagg, James Keeble, Angela Rodgers, Daphne E Lyonga, Graham R Stewart, Douglas B Young, Barry Walker, Tracy Hussell |
| Journal | The Journal of infectious diseases (J Infect Dis) Vol. 205 Issue 6 Pg. 975-83 (Mar 15 2012) ISSN: 1537-6613 [Electronic] United States |
| PMID | 22315280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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