ISSN:
1365-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Immunity against tuberculosis (TB), caused by Mycobacterium tuberculosis, depends largely on activation and maintenance of strong cell-mediated immune responses involving both CD4+ and CD8+ T cells and the ability to respond with Th1-type cytokines, particularly IFN-γ. Recent studies suggested that BCG, the only licensed vaccine against M. tuberculosis, may fail to induce T-cell responses in the lung mucosa and may therefore not protect against pulmonary TB. A decrease in TB mortality may be achieved by enhancing immunity in the lung. The present study evaluated the induction of antigen-specific immunity in the lung by intranasal (i.n.) delivery of the lipoprotein I (OprI) from Pseudomonas aeruginosa. OprI has shown to be a Toll-like receptor 2/4 agonist that, when given subcutaneously, induces Type-1 immune responses against heterologous antigens. Here, a fusion of OprI to Ag85A of Mtb (OprI-Ag85A) was used as a subunit vaccine in homologous prime-boost immunizations. In addition, OprI-Ag85A was combined with an Ag85A-encoding DNA vaccine (Ag85A DNA) or with BCG in heterologous prime-boost vaccinations. Intranasal and parenteral delivery with OprI-Ag85A elicited comparable T-cell responses in the spleen; in addition, i.n. delivery elicited specific T-cell responses in the lung lymph nodes (LLNs). Intramuscular delivery of Ag85A DNA induced significant systemic Th1 immune responses. Intranasal boosting with OprI-Ag85A enhanced this response and in addition induced an antigen-specific IFN-γ response in LLN. OprI may therefore be an efficient adjuvant for mucosal boosting. We continue to evaluate the protection induced by OprI-based prime-boost vaccinations against pulmonary TB. Results on the immunogenicity and protection against intravenous Mtb H37Rv infection will be presented.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0300-9475.2004.01423q.x
