Characterization of conserved combined T and B cell epitopes in Leptospira interrogans major outer membrane proteins OmpL1 and LipL41.
BACKGROUND
Leptospira interrogans are bacterial pathogens of animal that cause zoonotic infections in human. Outer membrane proteins of leptospire are among the most effective antigens which can stimulate remarkable immune responses during the infection processes, and thus are currently considered leading candidate vaccine antigens. The objective of the present study is to predict and confirm major combined B and T cell epitopes of leptospiral outer membrane proteins OmpL1 and LipL41, as well as to evaluate their capacity in the induction of immune responses in BALB/c mice.


RESULTS
In this study, four epitopes from OmpL1 and four from LipL41 conserved regions were evaluated for their potential utilization in leptospire vaccines. Firstly, combined B and T cell epitopes were predicted by softwares and expressed using a phage display system. OmpL1 residues 87-98 and 173-191 (OmpL187-98 and OmpL1173-191) and LipL4130-48, LipL41233-256 of LipL41 were identified as immunodominant B cell epitopes by Western blot. Epitopes OmpL1173-191, OmpL1297-320 of OmpL1 and LipL41233-256, LipL41263-282 of LipL41 were identified as immunodominant CD4+ T cell epitopes through proliferation analysis of splenocytes from recombinant OmpL1 (rOmpL1) or recombinant LipL41 (rLipL41)-immunized BALB/c (H-2d) mice. These epitopes induced responses of CD4+ T cells and Th1 (T helper cells) type cytokine responses during the infection.


CONCLUSIONS
This work identified combined T and B cell immunodominant epitopes in outer membrane proteins OmpL1 and LipL41 of Leptospira interrogans. OmpL1173-191 of OmpL1 and LipL41233-256 of LipL41 could be useful in a vaccine against Leptospira. The findings could also contribute to the development of effective cross-protective vaccine strategies for leptospirosis.
Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.
Xu'ai
X
Lin
Aihua
A
Sun
Ping
P
Ruan
Zhe
Z
Zhang
Jie
J
Yan
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology; D015153:Blotting, Western; D018985:Epitopes, B-Lymphocyte / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics*; D005260:Female; D007921:Leptospira interrogans / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction
D001425:Bacterial Outer Membrane Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte
J Assoc Physicians India. 2005 Jun;53:545-51
16121811
Biotechnol Annu Rev. 2004;10:151-88
15504706
Infect Immun. 2002 Dec;70(12):6926-32
12438371
Viral Immunol. 2005;18(4):678-88
16359234
Infect Immun. 1999 Dec;67(12):6572-82
10569777
J Leukoc Biol. 2004 Feb;75(2):163-89
14525967
Diagn Microbiol Infect Dis. 2009 Mar;63(3):237-42
19070450
Vaccine. 2000 Aug 15;19(1):86-94
10924790
BioDrugs. 2007;21(3):145-56
17516710
Curr Opin Infect Dis. 2005 Oct;18(5):376-86
16148523
Nature. 2003 Apr 24;422(6934):888-93
12712204
Vet Rec. 2002 Mar 30;150(13):420
11999287
Mol Med. 2003 Sep-Dec;9(9-12):209-19
15208742
J Allergy Clin Immunol. 2005 Aug;116(2):411-8
16083798
J Bacteriol. 2004 Apr;186(7):2164-72
15028702
Mem Inst Oswaldo Cruz. 2004;99(5 Suppl 1):63-6
15486637
Infect Immun. 2006 Jul;74(7):4172-9
16790792
J Biol Regul Homeost Agents. 2005 Jul-Dec;19(3-4):93-104
16602623
Bioinformatics. 2001 Dec;17(12):1236-7
11751237
PLoS One. 2008 Feb 13;3(2):e1607
18270594
J Immunol. 2009 Jun 15;182(12):7838-45
19494308
J Mol Biol. 1969 Jan;39(2):265-77
5362671
Nihon Rinsho. 2006 Jul;64(7):1269-74
16838643
J Bacteriol. 1993 Jul;175(13):4225-34
8320237
Curr Drug Targets. 2004 Jan;5(1):1-15
14738215
J Virol. 2003 Jun;77(11):6466-73
12743303
Microb Cell Fact. 2007 Dec 11;6:39
18072968
Infect Immun. 2009 Feb;77(2):799-809
19029301
Infect Immun. 1996 Jun;64(6):2322-30
8675344
BMC Microbiol. 2008 Dec 17;8:223
19087358
J Immunol. 2009 Jun 15;182(12):8047-55
19494330
Infect Immun. 2001 Dec;69(12):7550-8
11705932
FEMS Microbiol Rev. 2004 Jun;28(3):291-318
15449605
Immunity. 2009 May;30(5):646-55
19464987
Infect Immun. 2002 Jan;70(1):79-85
11748166
Clin Vaccine Immunol. 2010 May;17(5):778-83
20237196
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14560-5
16973745
Infect Immun. 2001 Aug;69(8):4958-68
11447174
Curr Opin Infect Dis. 2007 Jun;20(3):284-92
17471039
Clin Vaccine Immunol. 2008 Nov;15(11):1711-4
18827193
Expert Rev Mol Diagn. 2008 Jan;8(1):53-61
18088230