Immunomodulatory effects associated with a live vaccine against Leishmania major containing CpG oligodeoxynucleotides.

Abstract

The inoculation of live Leishmania major to produce a lesion that heals (leishmanization) is to date the only vaccine against cutaneous leishmaniasis that has proven effective in humans, but it still has an unacceptable frequency of large ulcerating lesions that are slow to heal or, in rare cases, non-healing. We have previously shown that C57BL/6 mice vaccinated intradermally with 10(4) L. major/50 microg CpG oligodeoxynucleotides develop little or no dermal lesions and show early containment of parasite growth in the vaccination site, eliminating safety concerns related to the inoculation of live organisms. The addition of CpG to the live vaccine resulted in early activation of dermal dendritic cells and increased IL-6 production, as well as in a reduction in the accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T (T(reg)) cells that naturally occurs in the skin following Leishmania infection. Neutralization of IL-6 caused the development of larger lesions and increased local T(reg) cell numbers. Transfer of vaccine-primed dendritic cells into IL-6-deficient mice mitigated lesion development, indicating that IL-6 reconstitution limited pathology in the vaccination site.

• Authors: Wenhui Wu, Luise Weigand, Yasmine Belkaid, Susana Mendez
• Journal: European journal of immunology (Eur J Immunol) Vol. 36 Issue 12 Pg. 3238-47 (Dec 2006) ISSN: 0014-2980 [Print] Germany
• PMID: 17109471 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Oligodeoxyribonucleotides
• Protozoan Vaccines
• Vaccines, Attenuated
• Vaccines, DNA

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Cells, Cultured
• CpG Islands (immunology)
• Leishmania major (immunology)
• Leishmaniasis, Cutaneous (immunology, therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oligodeoxyribonucleotides (immunology, therapeutic use)
• Protozoan Vaccines (immunology, therapeutic use)
• Vaccines, Attenuated (immunology, therapeutic use)
• Vaccines, DNA (immunology, therapeutic use)