A CD8+ T cell heptaepitope minigene vaccine induces protective immunity against Chlamydia pneumomiae

Irina Pinchuk, Barry C. Starcher, Brian Livingston, Amy Tvninnereim, Shiping Wu, Ettore Appella, John Sidney, Alessandro Sette, Benjamin Wizel

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

An intact T cell compartment and IFN-γ signaling are required for protective immunity against Chlamydia. In the mouse model of Chlamydia pneumoniae (Cpn) infection, this immunity is critically dependent on CD8 + T cells. Recently we reported that Cpn-infected mice generate an MHC class I-restricted CD8+ Tc1 response against various Cpn Ags, and that CD8+ CTL to multiple epitopes inhibit Cpn growth in vitro. Here, we engineered a DNA minigene encoding seven H-2b-restricted Cpn CTL epitopes, the universal pan-DR epitope Th epitope, and an endoplasmic reticulum-translocating signal sequence. Immunization of C57BL/6 mice with this construct primed IFN-γ-producing CD8+ CTL against all seven CTL epitopes. CD8+ T cell lines generated to minigene-encoded CTL epitopes secreted IFN-γ and TNF-α and exhibited CTL activity upon recognition of Cpn-infected macrophages. Following intranasal challenge with Cpn, a 3.6 log reduction in mean lung bacterial numbers compared with control animals was obtained. Using a 20-fold increase in the Cpn challenging dose, minigene-vaccinated mice had a 60-fold reduction in lung bacterial loads, compared with controls. Immunization and challenge studies with β2-microglobulin-/- mice indicated that the reduction of lung Cpn burdens was mediated by the MHC class I-dependent CD8+ T cells to minigene-included Cpn CTL epitopes, rather than by pan-DR epitope-speciflc CD4+ T cells. This constitutes the first demonstration of significant protection achieved by immunization with a CD8 + T cell epitope-based DNA construct in a bacterial system and provides the basis for the optimal design of multicomponent anti-Cpn vaccines for humans.

Original languageEnglish (US)
Pages (from-to)5729-5739
Number of pages11
JournalJournal of Immunology
Volume174
Issue number9
StatePublished - May 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pinchuk, I., Starcher, B. C., Livingston, B., Tvninnereim, A., Wu, S., Appella, E., Sidney, J., Sette, A., & Wizel, B. (2005). A CD8+ T cell heptaepitope minigene vaccine induces protective immunity against Chlamydia pneumomiae. Journal of Immunology, 174(9), 5729-5739.