title: KMP-11 DNA immunization significantly protects against L. donovani infection but requires exogenous IL-12 as an adjuvant for comparable protection against L. major.
abstract: As vaccine potential of cross-species protection by a candidate antigen is less explored, in this study we compared cross-specific protective efficacy of Kinetoplastid Membrane Protein-11 (KMP-11) as a DNA vaccine alone and in conjunction with exogenous IL-12 administration in experimental BALB/c model against two most widely prevalent forms of clinical diseases caused by Leishmania major (LM) and Leishmania donovani (LD). Whereas, KMP-11 DNA vaccination alone showed significant potential in terms of resolution of splenic and hepatic parasite burden against virulent LD challenge, it showed considerably less efficacy (<70% reduction) against virulent LM challenge in terms of presence of parasite in lymph node. Remarkably exogenous IL-12 administration in the form of IL-12 p35/p40 expression vectors or recombinant protein along with KMP-11 DNA had exactly opposing effect on protection against LM and LD. Exogenous IL-12 administration significantly increased residual LD-burden but enhanced the protective efficacy of KMP-11 DNA vaccine against LM compared to KMP-11 immunization alone. Elucidation of effector mechanism showed KMP-11 DNA induced protection against LD was associated with the generation of mixed Th1/Th2 response, while KMP-11/IL-12-induced comparable protection against LM was associated with high IgG2a titre indicative of a polarized Th1 response. Exogenous IL-12 administration resulted in robust gamma interferon (IFN-gamma) production and suppression of IL-4 from CD4+ T cell against both LM and LD. Nevertheless protective immune response was only compromised against LD infection where frequency of anti-KMP-11 CTL response was significantly reduced after exogenous IL-12 administration. Our study provides a comparative evaluation of effector mechanisms in the assessment of cross-specific protection by KMP-11 and KMP-11/IL-12 immunization against these two prevalent forms of leishmaniasis.
authors.affiliation: Department of Immunology, Indian Institute of Chemical Biology (IICB), 4, Raja S.C. Mullick Road, Jadavpur, Calcutta, 700032, WB, India.
authors.forename: Suniti
authors.initials: S
authors.lastname: Bhaumik
authors.forename: Rajatava
authors.initials: R
authors.lastname: Basu
authors.forename: Subha
authors.initials: S
authors.lastname: Sen
authors.forename: Kshudiram
authors.initials: K
authors.lastname: Naskar
authors.forename: Syamal
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D016053:RNA, Protozoan / Q000235:genetics / Q000302:isolation & purification
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C090009:kinetoplastid membrane protein 11, Leishmania donovani