Heterologous Prime-Boost Vaccination with the LACK Antigen Protects against Murine Visceral Leishmaniasis

Dondji, Blaise; Pérez-Jiménez, Eva; Goldsmith-Pestana, Karen; Esteban, Mariano; McMahon-Pratt, Diane

doi:10.1128/iai.73.8.5286-5289.2005

Cited by 70 publications

(47 citation statements)

References 47 publications

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“…Rather than replication-incompetent MVA, Gonzalo utilized the replication-competent Western Reserve strain of vaccinia virus, which influenced the longevity of viral expression in target organs and subsequent immunogenicity, especially with respect to cross-reacting viral antigens (24,25). A recent comparison of heterologous boosting with the Western Reserve strain and boosting with MVA expressing LACK in a visceral leishmaniasis model revealed that there were more potent Th1-Th2/T reg (IFN-␥-IL-10) responses for the Western Reserve strain before challenge, although the levels of protection were equivalent for the two viral strains (5).…”

Section: Vol 75 2007mentioning

confidence: 99%

Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory againstLeishmania majorin Susceptible BALB/c Mice

et al. 2007

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Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYPmodified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-␥) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-␥, sustained prechallenge levels of memory phase IFN-␥, and a more polarized post-L. major challenge Th1 response compared to the Th2/T reg response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.Leishmaniasis is caused by intracellular protozoan parasites transmitted by the bite of a sand fly, and the diverse clinical manifestations range from localized cutaneous lesions to fatal visceral infection. The disease prevalence is estimated to be 12 million people, and there are 1.5 million new cases annually. There are no vaccines in routine use. Experimental infections of inbred mice with Leishmania major defined the Th1/Th2 paradigm (for reviews, see references 16 and 26) and demonstrated that primary immunity to L. major in resistant mice requires the development of a polarized Th1 response (11,31,32). In contrast, susceptibility in BALB/c mice was associated with an aberrant Th2 response resulting from the early production of interleukin-4 (IL-4) by a restricted population of V␤4V␣8 CD4 ϩ T cells (12, 13). These studies supported the hypothesis that immunotherapy shifting the balance from IL-4 to gamma interferon (IFN-␥) would provide the key to vaccine success. The challenge for developing a vaccine against Leishmania spp., like the challenge for developing vaccines against other intracellular pathogens, such as Mycobacterium tuberculosis, is thought to be induction and maintenance of a cellmediated immune response that produces IFN-␥ to activate macrophages to kill the pathogen.The vaccination strategies employed to induce protective immunity in experimental models of leishmaniasis have included vaccination with recombinant Leishmania antigens, such as a Leishmania homologue of the receptor for activated C kinase (LACK) plus IL-12 as an adjuvant, vaccination with live attenuated parasites, vaccination with plasmid DNA encoding single or multiple parasite antigens, and vaccination with live recombinant vectors, such as Salmonella spp., Mycobacterium bovis BCG, or vaccinia virus (for a review, see reference 19). While all of these studies have resulted in some degree of...

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Section: Vol 75 2007mentioning

confidence: 99%

Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory againstLeishmania majorin Susceptible BALB/c Mice

et al. 2007

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“…Therefore, efforts to introduce a new protein for vaccine production are currently being considered. Up to now, various antigens such as TSA, and P4 LACK, have been evaluated for vaccine development (5)(6)(7)(8)(9). In this regard, a new molecule common in Leishmania species, is the 11KD protein of the membrane kinetoplastid surface or KMP-11 (10).…”

Section: Introductionmentioning

confidence: 99%

Molecular Cloning and Expression of the Leishmania infantum KMP-11 Gene

Soflaei

Dalimi

Ghafarifar

2013

Jundishapur J Microbiol

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“…Virus-based vaccines may be particularly suited to induce CD8 + T cells. Experience in other fields 63 and the results of several studies that explored experimental anti-Leishmania vaccines 57,59,64,65 suggest that prime boost combinations with heterologous vaccine formulations offer synergies that may become very important. We choose to refine the approach of using recombinant, live salmonella (see Fig.…”

Section: Vaccine Formulationsmentioning

confidence: 99%