KMP-11 DNA immunization significantly protects against L. donovani infection but requires exogenous IL-12 as an adjuvant for comparable protection against L. major

被引:50
作者
Bhaumik, Suniti [1 ]
Basu, Rajatava [1 ]
Sen, Subha [1 ]
Naskar, Kshudiram [1 ]
Roy, Syamal [1 ]
机构
[1] Indian Inst Chem Biol, Dept Immunol, Kolkata 700032, W Bengal, India
关键词
DNA vaccination; Parasitic-protozoan; Th1/Th2; cells; EXPERIMENTAL VISCERAL LEISHMANIASIS; HUMAN CUTANEOUS LEISHMANIASIS; T-CELL RESPONSES; IMMUNE-RESPONSE; MEMORY CD4(+); C57BL/6; MICE; IFN-GAMMA; VACCINE; INTERLEUKIN-12; TH1;
D O I
10.1016/j.vaccine.2008.12.053
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 LID 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. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1306 / 1316
页数:11
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