Induction of targeted CD8+-mediated immunity for the design of epitope vaccines

Projektinformationen

ID Finanzhilfevereinbarung: BIO4960152

Projekt abgeschlossen

Startdatum 1 November 1996

Enddatum 29 Februar 2000

Finanziert unter

• Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998

Gesamtkosten € 0,00

EU-Beitrag Keine Daten

Koordiniert durch

NATIONAL PUBLIC HEALTH INSTITUTE
Finland

Exploitable results

Production and purification of proteins derived from Chlamydia pneumoniae in Bacillus for use as immunologic reagents

Chlamydia pneumoniae, an obligatory intracellular pathogen, is difficult to grow in large quantities and consequently it is usually not possible to obtain its components in a pure form. Production of the C. pneumoniae proteins is therefore best done in a heterologous host; however, the most commonly used host, E. coli, contains endotoxin that is often difficult to remove from the proteins and, because of its biological activities, often interferes with the use of the proteins of interest in biological systems. This is particularly true of bioassays using human or animal cells. We therefore exploited the use of the Gram-positive Bacillus subtilis as the production host and obtained several C. pneumoniae proteins in a pure state applicable to use as antigen in immunoassays. Such C. pneumoniae assays may become interesting diagnostic assays to select patients for prophylactic or therapeutic approaches related to the association of C. pneumoniae with cardiovascular diseases. R & D towards such applications is in progress.

Protective immunity to Chlamydia pneumoniae: Importance of CD8+ cells and gamma-interferon; identification of protective antigens

We have demonstrated that CD8+ T cells and gamma-interferon (typical to Th1 type response) are essential for protective immunity to Chlamydia pneumoniae, an intracellular pathogen for which no vaccine is available. This knowledge is essential for development of vaccines and/or immunotherapeutic agents, and led us to focus on means to specifically stimulate the CD8+ cells. One of such means is immunization with "naked DNA"; with this approach we could show protective activity by several C. pneumoniae proteins. Further R&D is in process.

Identification and characterization of putative CD8+ T-cell stimulating epitopes (mouse & human) derived from Chlamydia pneumoniae

No vaccines against the important pathogen Chlamydia pneumoniae exist so far. In preliminary work we have shown that so called CD8+ T cells are essential for protection against this pathogen. However, a problem has been in how to stimulate these important immune system cells. In this project, as a step towards developing an effective vaccine against Chlamydia pneumoniae we identified a number of peptides corresponding to several proteins of Chlamydia pneumoniae that are either shown to stimulate CD8+ cells or highly likely to do so. Such peptides are called CD8 cell epitopes and could be exploited as vaccine antigens in a number of ways, notably as peptide vaccines or as DNA sequences to be presented either as "naked DNA" or part of specific vectors. We have pursued these approaches (Result 2) and continue to do so towards a vaccine for C. pneumoniae.