A novel recombinant Leishmania donovani p45, a partial coding region of methionine aminopeptidase, generates protective immunity by inducing a Th1 stimulatory response against experimental visceral leishmaniasis

被引:24
作者
Gupta, Reema [1 ]
Kushawaha, Pramod K. [1 ]
Tripathi, Chandra Dev Pati [1 ]
Sundar, Shyam [2 ]
Dube, Anuradha [1 ]
机构
[1] Cent Drug Res Inst, Div Parasitol, Lucknow 226001, Uttar Pradesh, India
[2] Benaras Hindu Univ, Dept Med, Inst Med Sci, Varanasi, Uttar Pradesh, India
关键词
Leishmania donovani; Recombinant p45; Methionine aminopeptidase; Immunogenicity; T-cell response; Cured Leishmania hamsters; Cured Leishmania patients and endemic contacts; Prophylactic potential; NITRIC-OXIDE; CELLULAR-RESPONSES; INFECTED PATIENTS; IFN-GAMMA; 97.1; KDA; ANTIGENS; IDENTIFICATION; PROMASTIGOTES; HAMSTERS; BCG;
D O I
10.1016/j.ijpara.2012.02.013
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
The development of a vaccine against visceral leishmaniasis (VL) conferring long-lasting immunity remains a challenge. Identification and proteomic characterization of parasite proteins led to the detection of p45, a member of the methionine aminopeptidase family. To our knowledge the present study is the first known report that describes the molecular and immunological characterization of p45. Recombinant Leishmania donovani p45 (rLdp45) induced cellular responses in cured hamsters and generated Th1-type cytokines from peripheral blood mononuclear cells of cured/endemic VL patients. Immunization with rLdp45 exerted considerable prophylactic efficacy (similar to 85%) supported by an increase in mRNA expression of iNOS, IFN-gamma, TNF-alpha and IL-12 and decrease in TGF-beta and IL-4, indicating its potential as a vaccine candidate against VL. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:429 / 435
页数:7
相关论文
共 23 条
[1]   Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity against Leishmania donovani Infection [J].
Bhowmick, Sudipta ;
Mazumdar, Tuhina ;
Ali, Nahid .
INFECTION AND IMMUNITY, 2009, 77 (04) :1514-1523
[2]  
CARVALHO EM, 1994, J IMMUNOL, V152, P5949
[3]   T cell response of asymptomatic Leishmania chagasi infected subjects to recombinant leishmania antigens [J].
Costa, SR ;
Júnior, AD ;
Bacellar, O ;
Carvalho, EM .
MEMORIAS DO INSTITUTO OSWALDO CRUZ, 1999, 94 (03) :367-370
[4]   Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani [J].
Garg, R ;
Gupta, SK ;
Tripathi, P ;
Naik, S ;
Sundar, S ;
Dube, A .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2005, 140 (01) :149-156
[5]   Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes [J].
Gupta, Shraddha Kumari ;
Sisodia, Brijesh Singh ;
Sinha, Sudhir ;
Hajela, Krishnan ;
Naik, Sita ;
Shasany, Ajit Kumar ;
Dube, Anuradha .
PROTEOMICS, 2007, 7 (05) :816-823
[6]   RECOMBINANT INTERLEUKIN-12 CURES MICE INFECTED WITH LEISHMANIA-MAJOR [J].
HEINZEL, FP ;
SCHOENHAUT, DS ;
RERKO, RM ;
ROSSER, LE ;
GATELY, MK .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (05) :1505-1509
[7]   POTENTIAL ROLE FOR INTERLEUKIN-10 IN THE IMMUNOSUPPRESSION ASSOCIATED WITH KALA-AZAR [J].
HOLADAY, BJ ;
POMPEU, MMD ;
JERONIMO, S ;
TEXEIRA, MJ ;
SOUSA, AD ;
VASCONCELOS, AW ;
PEARSON, RD ;
ABRAMS, JS ;
LOCKSLEY, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (06) :2626-2632
[8]   Leishmania major: common antigen responsible for induction of delayed-type hypersensitivity response in guinea pigs [J].
Khabiri, A. R. ;
Bagheri, F. ;
Assmar, M. .
PARASITOLOGY RESEARCH, 2007, 100 (03) :629-632
[9]   Leishmania major:: Species specific delayed hypersensitivity reaction induced by exogenous secreted antigen in the guinea pig [J].
Khabiri, AR ;
Bagheri, F ;
Assmar, M .
EXPERIMENTAL PARASITOLOGY, 2006, 112 (03) :184-186
[10]   Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis:: a randomised, double-blind, BCG-controlled trial in Sudan [J].
Khalil, EAG ;
El Hassan, AM ;
Zijlstra, EE ;
Mukhtar, MM ;
Ghalib, HW ;
Musa, B ;
Ibrahim, ME ;
Kamil, AA ;
Elsheikh, M ;
Babiker, A ;
Modabber, F .
LANCET, 2000, 356 (9241) :1565-1569