title: Co-administration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral leishmaniaisis.
abstract: Visceral leishmaniasis, caused by the intracellular parasite Leishmania donovani is a significant public health problem in many regions of the world. Anti-leishmanial immune defences are primarily dependent on the ability of the host to mount an interleukin-12 (IL-12) driven Th1 type of responses. Thus, IL-12 plays a pivotal role in diversification of the immune responses towards Th1 type. In this report, we investigated the effect of IL-12 DNA as an adjuvant with leishmanial recombinant open reading frame F (rORFF) protein. We demonstrate that an expression plasmid encoding both p35 and p40 subunits of IL-12 when co-administered with rORFF induces a significant protection with around 82% protection in both liver and spleen. The protection correlated with increased proliferative response of splenocytes and subsequent release of Th1 cytokine IFN-gamma. The levels of IFN-gamma were sustained 4 and 8 weeks after challenge with L. donovani promastigotes. Interestingly, IL-12 DNA played a key role in modulating the antibody response towards IgG2a isotype suggesting its use as a potential vaccine adjuvant against intracellular infections like leishmaniasis.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Tewary
authors.forename: Shailendra
authors.initials: S
authors.lastname: Saxena
authors.forename: Rentala
authors.initials: R
authors.lastname: Madhubala
mesh_terms: D000818:Animals; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C402106:ORFF protein, Leishmania; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D007371:Interferon-gamma