The Leishmania infantum acidic ribosomal protein P0 administered as a DNA vaccine confers protective immunity to Leishmania major infection in BALB/c mice

被引:53
作者
Iborra, S
Soto, M
Carrión, J
Nieto, A
Fernández, E
Alonso, C
Requena, JM [1 ]
机构
[1] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain
[2] Univ Complutense Madrid, Fac Vet, Dept Patol Anim 2, Madrid, Spain
关键词
D O I
10.1128/IAI.71.11.6562-6572.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, we examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0) were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like Immoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-gamma) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection against L. major infection was achieved, as determined by both lesion development and parasite burden. Immunization of mice with LiP0-DNA primes both CD4(+) and CD8(+) T cells, which, with the L. major challenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-gamma. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.
引用
收藏
页码:6562 / 6572
页数:11
相关论文
共 33 条
[1]   CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major [J].
Belkaid, Y ;
Von Stebut, E ;
Mendez, S ;
Lira, R ;
Caler, E ;
Bertholet, S ;
Udey, MC ;
Sacks, D .
JOURNAL OF IMMUNOLOGY, 2002, 168 (08) :3992-4000
[2]   CULTURE MICROTITRATION - A SENSITIVE METHOD FOR QUANTIFYING LEISHMANIA-INFANTUM IN TISSUES OF INFECTED MICE [J].
BUFFET, PA ;
SULAHIAN, A ;
GARIN, YJF ;
NASSAR, N ;
DEROUIN, F .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (09) :2167-2168
[3]   Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion proteins confers protection against Leishmania major infection in susceptible BALB/c mice [J].
Campos-Neto, A ;
Webb, JR ;
Greeson, K ;
Coler, RN ;
Skeiky, YAW ;
Reed, SG .
INFECTION AND IMMUNITY, 2002, 70 (06) :2828-2836
[4]   Leishmania model for microbial virulence:: the relevance of parasite multiplication and pathoantigenicity [J].
Chang, KP ;
Reed, SG ;
McGwire, BS ;
Soong, L .
ACTA TROPICA, 2003, 85 (03) :375-390
[5]   Antibodies against ribosomal phosphoprotein PO of Plasmodium falciparum protect mice against challenge with Plasmodium yoelii [J].
Chatterjee, S ;
Singh, S ;
Sohoni, R ;
Singh, NJ ;
Vaidya, A ;
Long, C ;
Sharma, S .
INFECTION AND IMMUNITY, 2000, 68 (07) :4312-4318
[6]   Characterization of domains of the phosphoriboprotein P0 of Plasmodium falciparum [J].
Chatterjee, S ;
Singh, S ;
Sohoni, R ;
Kattige, V ;
Deshpande, C ;
Chiplunkar, S ;
Kumar, N ;
Sharma, S .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2000, 107 (02) :143-154
[7]   MECHANISM AND REGULATION OF IMMUNOGLOBULIN ISOTYPE SWITCHING [J].
COFFMAN, RL ;
LEBMAN, DA ;
ROTHMAN, P .
ADVANCES IN IMMUNOLOGY, VOL 54, 1993, 54 :229-270
[8]   Immunization with a polyprotein vaccine consisting of the T-cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis [J].
Coler, RN ;
Skeiky, YAW ;
Bernards, K ;
Greeson, K ;
Carter, D ;
Cornellison, CD ;
Modabber, F ;
Campos-Neto, A ;
Reed, SG .
INFECTION AND IMMUNITY, 2002, 70 (08) :4215-4225
[9]   Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination:: A potential immunoregulatory role for CD8+ T cells [J].
Gurunathan, S ;
Stobie, L ;
Prussin, C ;
Sacks, DL ;
Glaichenhaus, N ;
Fowell, DJ ;
Locksley, RM ;
Chang, JT ;
Wu, CY ;
Seder, RA .
JOURNAL OF IMMUNOLOGY, 2000, 165 (02) :915-924
[10]   DNA vaccines: Immunology, application, and optimization [J].
Gurunathan, S ;
Klinman, DM ;
Seder, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :927-974