Vaccination with the Leishmania major ribosomal proteins plus CpG oligodeoxynucleotides induces protection against experimental cutaneous leishmaniasis in mice.
In the present work we analyze the antigenicity of Leishmania major ribosomal proteins (LRP) in infected BALB/c mice. We show that BALB/c mice vaccinated with LRP in the presence of CpG oligodeoxynucleotides (CpG-ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load after challenge with L. major. This protection was associated with the induction of an IL-12 dependent specific-IFN-gamma response mediated mainly by CD4(+) T cell, albeit a minor contribution of CD8(+) T cells cannot be ruled out. Induction of Th1 responses against LRP also resulted in a reversion of the Th2 responses associated with susceptibility. A marked reduction of IgG1 antibody titer against parasite antigens besides an impaired IL-4 and IL-10 cytokine production by parasite specific T cells was observed. In addition, we show that the administration of the LRP plus CpG-ODN preparation also conferred protection in the naturally resistant C57BL/6 mice. In this strain protection was associated with a LRP specific IFN-gamma production in lymph nodes draining the challenge site. We believe that these evolutionary conserved proteins, combined with adjuvants that favor Th1 responses, may be relevant components of a pan-Leishmania vaccine.
Iborra
Salvador
S
Unidad de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Crta. Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain.
Parody
Nuria
N
Abánades
Daniel R
DR
Bonay
Pedro
P
Prates
Deboraci
D
Novais
Fernanda O
FO
Barral-Netto
Manoel
M
Alonso
Carlos
C
Soto
Manuel
M
D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D054332:Leishmaniasis Vaccines; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins; D012269:Ribosomal Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma