Specific cellular and humoral immune response in Balbc mice immunised with an expression genomic library of Trypanosoma cruzi

Alberti, Esteban; Acosta, Armando; Sarmiento, María E.; Hidalgo, Carlos; Vidal, Teresita; Fachado, Alberto; Fonte, Luis; Izquierdo, Luís; Infante, Juan F.; Finlay, Carlos M.; Sierra, Gustavo

doi:10.1016/s0264-410x(97)00228-4

Cited by 32 publications

(14 citation statements)

References 16 publications

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“…The effectiveness of T. cruzi genes as genetic vaccines for the elicitation of parasite-specific immune responses has recently been shown in a number of laboratories with several different T. cruzi genes (1,4,11,21,27,30,36). We have demonstrated the utility of TSA-1-encoding plasmids as genetic vaccines for the elicitation of T. cruzi-specific immune FIG.…”

Section: Discussionmentioning

confidence: 88%

“…The studies described above, as well as previously published results (1,4,11,21,27,30,36), demonstrate that genetic immunization However, none of these previous studies addressed the question of whether or not such vaccinations alter the course of disease development in the chronic phase of infection. For this analysis, sections from heart and skeletal muscles from mice immunized and challenged with 10 5 BFT were assessed at various time intervals for tissue parasite burden and inflammation.…”

Section: Expression Of T Cruzi Genes In Cos Cellsmentioning

confidence: 96%

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Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity inTrypanosoma cruziInfection

2002

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Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated immune responses to extracellular trypomastigotes and intracellular amastigotes. In this study, the effectiveness of the T. cruzi trans-sialidase family (ts) genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses. Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL activity and antibody production and in increased resistance to T. cruzi infection. In pooled results from two to four experiments, 30 to 60% of mice immunized with antigen-encoding plasmids and 60 to 80% of mice immunized with antigen-encoding plasmids plus cytokine adjuvants survived a lethal challenge with T. cruzi. In comparison, 90% of control mice injected with empty plasmid DNA died during the acute phase of infection. However, the pool of three ts genes provided no greater protection than the most effective single gene (ASP-2) either with or without coadministration of cytokine plasmids. Importantly, the extent of tissue parasitism, inflammation, and associated tissue damage in skeletal muscles during the chronic phase of T. cruzi infection in mice immunized with antigen-encoding plasmids plus cytokine adjuvants was remarkably reduced compared to mice immunized with only cytokine adjuvants or empty plasmid DNA. These results identify new vaccine candidates and establish some of the methodologies that might be needed to develop effective vaccine-mediated control of T. cruzi infection. In addition, this work provides the first evidence that prophylactic genetic immunization can prevent the development of Chagas' disease.

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Section: Discussionmentioning

confidence: 88%

Section: Expression Of T Cruzi Genes In Cos Cellsmentioning

confidence: 96%

Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity inTrypanosoma cruziInfection

2002

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“…ELI has been applied to bacterial (3,7) and parasitic (1,24,28,31) infections and recently to simian immunodeficiency virus infection (32). Genomic ELI libraries encode antigens from all stages of the life cycle, potentially allowing the discovery of antigens from particular stages of a life cycle.…”

mentioning

confidence: 99%

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

et al. 2003

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It has been proposed that a multivalent malaria vaccine is necessary to mimic the naturally acquired resistance to this disease observed in humans. A major experimental challenge is to identify the optimal components to be used in such a multivalent vaccine. Expression library immunization (ELI) is a method for screening genomes of a pathogen to identify novel combinations of vaccine sequences. Here we describe immune responses associated with, and the protective efficacy of, genomic Plasmodium chabaudi adami DS expression libraries constructed in VR1020 (secretory), monocyte chemotactic protein-3 (chemoattractant), and cytotoxic T lymphocyte antigen 4 (lymph node-targeting) DNA vaccine vectors. With splenocytes from vaccinated mice, specific T-cell responses, as well as gamma interferon and interleukin-4 production, were observed after stimulation with P. chabaudi adami-infected erythrocytes, demonstrating the specificity of genomic library vaccination for two of the three libraries constructed. Sera obtained from mice vaccinated with genomic libraries promoted the opsonization of P. chabaudi adami-infected erythrocytes by murine macrophages in vitro, further demonstrating the induction of malaria-specific immune responses following ELI. Over three vaccine trials using biolistic delivery of the three libraries, protection after lethal challenge with P. chabaudi adami DS ranged from 33 to 50%. These results show that protective epitopes or antigens are expressed within the libraries and that ELI induces responses specific to P. chabaudi adami malaria. This study further demonstrates that ELI is a suitable approach for screening the malaria genome to identify the components of multivalent vaccines.

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“…Another approach in DNA immunisation is the use of whole genomic expression libraries of microorganisms, in order to identify relevant antigens for protection [74]. We observed that immunisation of mice with a genomic expression library of M. tuberculosis resulted in specific antibody responses recognizing proteins of M. tuberculosis and BCG by Western blotting, and studies are underway to evaluate the protective capability of the administration of the genomic library in mice [5].…”

Section: Dna Vaccinesmentioning

confidence: 99%

Recent Advances in Tuberculosis Vaccine Development

Nor¹,

Sarmiento²,

Acosta

2005

CRMR

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Tuberculosis is exacting a great toll on the lives of many people worldwide. Despite seemingly previous successes in controlling the disease, tuberculosis is now re-emerging as the leading cause of mortality due to infectious diseases in many parts of the world. The high incidence of the disease has been attributed mainly to its combination with HIV infection and the emergence of multi-drug resistant strains. In addition, the low diagnostic reliability and therapeutic coverage, as well as the absence of a fully protective vaccine, configure the current situation of the disease at a worrying level. Taking into account these antecedents, it is considered that the development of an effective vaccine is the most important and urgent element for the control of the disease. Supported by the better understanding of the immune response to the infection, the biology of Mycobacterium tuberculosis and the availability of new technologies in genomics and proteomics, a wide range of experimental vaccines have been attempted. These approaches include the use of inactivated strains; live genetically attenuated strains; live vectors expressing M. tuberculosis antigens; recombinant subunits, conjugated, and DNA vaccines as well as the combination of selected strategies in prime boost immunisations. Furthermore, the use of novel adjuvants, delivery systems and routes of immunisation have also been evaluated. Some of the candidate vaccines demonstrated significant levels of efficacy in animal models and are now in initial clinical evaluation. This review analyzes the main aspects related to the development of new generation vaccines against tuberculosis, as well as the challenges and complexities inherent to this endeavour.

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Specific cellular and humoral immune response in Balbc mice immunised with an expression genomic library of Trypanosoma cruzi

Cited by 32 publications

References 16 publications

Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity inTrypanosoma cruziInfection

Genetic Immunization Elicits Antigen-Specific Protective Immune Responses and Decreases Disease Severity inTrypanosoma cruziInfection

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

Recent Advances in Tuberculosis Vaccine Development

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