The combination of DNA vectors expressing IL-12 + IL-18 elicits high protective immune response against cutaneous leishmaniasis after priming with DNA-p36/LACK and the cytokines, followed by a booster with a vaccinia virus recombinant expressing p36/LACK.

Abstract

Protocols of immunization based on the DNA prime/vaccinia virus (VV) boost regime with recombinants expressing relevant antigens have been shown to elicit protection against a variety of pathogens in animal model systems, and various phase I clinical trials have been initiated with this vaccination approach. We have previously shown that mice immunized with a DNA vector expressing p36/LACK of Leishmania infantum followed by a booster with VVp36/LACK induced significant protection against Leishmania major infection. To further improve this protocol of immunization, here we investigated whether the cytokines interleukin-12 (IL-12) and IL-18 could enhance protection against L. major infection in BALB/c mice. We found that priming with DNA vectors expressing p36/LACK and either IL-12 or IL-18, followed by a booster with a VV recombinant expressing the same L. infantum LACK antigen, elicit a higher cellular immune response than by using the same protocol in the absence of the cytokines. The cytokine IL-12 triggered a higher number of IFN-gamma-secreting cells specific for p36 protein than IL-18. When immunized animals were challenged with promastigotes, the highest protection against L. major infection was observed in animals primed with DNAp36 + DNA IL-12 + DNA IL-18 and boosted with VVp36. This protection correlated with a Th1 type of immune response. Our findings revealed that in prime/booster protocols, co-expressing IL-12 and IL-18 during priming is an efficient approach to protect against leishmaniasis. This combined prime/booster immunization regime could have wide use in fighting against parasitic and other infectious diseases.

• Authors: Esther Tapia, Eva Pérez-Jiménez, Laura López-Fuertes, Rosa Gonzalo, M Magdalena Gherardi, Mariano Esteban
• Journal: Microbes and infection (Microbes Infect) Vol. 5 Issue 2 Pg. 73-84 (Feb 2003) ISSN: 1286-4579 [Print] France
• PMID: 12650765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Interleukin-18
• Protozoan Proteins
• Protozoan Vaccines
• Vaccines, DNA
• LACK antigen, Leishmania
• Interleukin-12

Topics

• Animals
• Antibodies, Protozoan (blood)
• Antigens, Protozoan
• Female
• Genetic Vectors
• Immunization
• Immunization Schedule
• Immunization, Secondary
• Interleukin-12 (genetics, immunology, metabolism)
• Interleukin-18 (genetics, immunology, metabolism)
• Leishmania infantum (immunology)
• Leishmania major (pathogenicity)
• Leishmaniasis, Cutaneous (immunology, parasitology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Protozoan Proteins (genetics, immunology)
• Protozoan Vaccines (administration & dosage, immunology)
• Th1 Cells (immunology)
• Vaccines, DNA (immunology)
• Vaccinia virus (genetics)