A single intradermal administration of soluble leishmanial antigen and plasmid expressing interleukin-12 protects BALB/c mice from Leishmaniamajor infection

• Published in: Parasitology international Vol. 50; no. 2; pp. 81 - 91
• Main Authors: Yamakami, Kazuo, Akao, Shinkichi, Sato, Masaki, Nitta, Yoshio, Miyazaki, Jyun-ichi, Tadakuma, Takushi
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 2001
• Subjects: IL-12; Leishmania major; Mice; Plasmid; Th1/2; Vaccination; Plasmid; IFN, interferon; SLA, soluble leishmanial antigen; Vaccination; IL, interleukin; Mice; IL-12; ELISA, enzyme-linked immunosorbent assay; Leishmania major; Th1/2
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/S1383-5769(01)00070-8

In murine leishmaniasis, the induction of the T-helper type 1 (Th1) response contributes to infection resistance, whereas the establishment of the Th2 response makes the mice susceptible to infection. Interleukin-12 (IL-12) plays a pivotal role in the diversification of immune responses to the Th1 type. In this study, we tested whether the co-administration of IL-12 expression plasmid which compose p35 and p40 subunits and soluble leishmanial antigen (SLA) will skew the susceptible BALB/c mice to Th1 response and protect from leishmaniasis. When the mice were intradermally injected with the combination of IL-12 plasmid and SLA 7 days prior to the challenge with 1×10 6 promastigotes of Leishmania major, the local lesions completely healed and the parasite burden in the local lymph nodes significantly decreased. The cured mice attained long-term immunity, and were resistant to any subsequent rechallenge of the lethal dose of the parasite. The protective effect was associated with the development of a Th1 response, as demonstrated by the enhanced level of antigen-specific interferon-γ (IFN-γ) and dominant production of IgG2a in the serum. In contrast, the administration of empty plasmid plus SLA or IL-12 plasmid alone failed to protect the disease and shape the Th1 response. Furthermore, the protective efficiency induced by the vaccination was clearly prevented by the injection of either neutralizing anti-IL-12 mAb or anti-IFN-γ mAb. The IL-12 expression plasmid is thus an effective adjuvant for the elicitation of a protective Th1 response against leishmaniasis and is therefore, considered to be appropriate for vaccinations that require the induction of Th1 type immunity.