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OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection.

Snelgrove, RJ, Cornere, MM, Edwards, L, Dagg, B, Keeble, J, Rodgers, A, Lyonga, DE, Stewart, GR, Young, DB, Walker, B and Hussell, T (2012) OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection. Journal of Infectious Diseases, 205 (6). pp. 975-983.

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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.

Item Type: Article
Authors :
NameEmailORCID
Snelgrove, RJUNSPECIFIEDUNSPECIFIED
Cornere, MMUNSPECIFIEDUNSPECIFIED
Edwards, LUNSPECIFIEDUNSPECIFIED
Dagg, BUNSPECIFIEDUNSPECIFIED
Keeble, JUNSPECIFIEDUNSPECIFIED
Rodgers, AUNSPECIFIEDUNSPECIFIED
Lyonga, DEUNSPECIFIEDUNSPECIFIED
Stewart, GRUNSPECIFIEDUNSPECIFIED
Young, DBUNSPECIFIEDUNSPECIFIED
Walker, BUNSPECIFIEDUNSPECIFIED
Hussell, TUNSPECIFIEDUNSPECIFIED
Date : 15 March 2012
Identification Number : 10.1093/infdis/jir868
Uncontrolled Keywords : Animals, Antigen-Presenting Cells, BCG Vaccine, CD8-Positive T-Lymphocytes, Cell Proliferation, Female, Killer Cells, Natural, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Recombinant Fusion Proteins, T-Lymphocytes, Th1 Cells, Tuberculosis, Tumor Necrosis Factors, Vaccination
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 13:43
Last Modified : 31 Oct 2017 14:57
URI: http://epubs.surrey.ac.uk/id/eprint/745930

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