A mucosally administered recombinant fusion protein vaccine against schistosomiasis protecting against immunopathology and infection

Lebens, Michael; Sun, Jiabin; Sadeghi, Hamid Mirmohammad; Bäckström, Malin; Olsson, Ida; Mielcarek, Nathalie; Li, Bin-Ling; Càpron, André; Czerkinsky, Cécil; Holmgren, Jan

doi:10.1016/s0264-410x(02)00471-1

Cited by 35 publications

(26 citation statements)

References 33 publications

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“…Once efficacy has been proven with Freund's adjuvants, other adjuvants, particularly those that are licensed (or have the potential for licensing) for human use, should be used to formulate an antigen. Less conventional or less widely used approaches have been explored as adjuvants for schistosome vaccines, including live Salmonella (113), tetanus toxin (2), filamentous phages (124), recombinant Mycobacterium bovis BCG (151,152), nanoparticles (46), and various methods of mucosal delivery (88,121,140).…”

Section: Antigen Formulation and Delivery Of Vaccines Against Schistomentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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SUMMARY Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality. Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite. Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations. In particular, mass treatment does not prevent reinfection. Furthermore, there is increasing concern about the development of parasite resistance to PZQ. Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy. An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible. This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against the African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack.

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Section: Antigen Formulation and Delivery Of Vaccines Against Schistomentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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“…In many preclinical studies mucosal administration of antigens (Ag) linked to CTB has been shown to represent a very efficacious way of inducing peripheral tolerance (so-called oral tolerance) and thus suppressing the development of autoimmune or allergic reactions involving the coupled or bystander Ag [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. The mechanisms for the strong potentiation of oral tolerance induction by using CTB-coupled Ag and not fully understood but appear to include the following CTB-mediated effects: (i) increased uptake of Ag across the mucosal barrier, (ii) increased Ag binding, uptake and presentation by DC and other APC, and (iii) providing selected DC (and other APC?)…”

Section: Use Of Ctb For Mucosal Immunotherapy With Proof-of-principlementioning

confidence: 99%

Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA

et al. 2005

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“…The lower antibody levels could be a problem, since protection in a sepsis model is attributed to the presence of IgG in the serum, which is corroborated by the efficiency of passive immunization at protecting mice from fatal infection with S. pneumoniae (6,16). CTB has proved to be a good adjuvant for different antigens when administered through the mucosa (9,10). More recently, some groups have published the adjuvant effect of CTB when inoculated through the skin, such as the transcutaneous or epidermal route (1,7), by a Th1-predominant mechanism.…”

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Intradermal Immunization of Mice with Cholera Toxin B-Pneumococcal Surface Protein A Fusion Protein Is Protective against Intraperitoneal Challenge with Streptococcus pneumoniae

et al. 2005

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Cholera toxin B subunit is known for its adjuvant properties when associated with different antigens. In this work, we have fused the ctxB gene to the pneumococcal surface protein (pspA) gene from Streptococcus pneumoniae. Intradermal administration of the fusion protein in mice induced anti-PspA antibodies and protection against pneumococcus in a sepsis model.Streptococcus pneumoniae is the major cause of bacterial pneumonia, meningitis, and otitis media cases around the world, leading to up to 1 million deaths per year. Pneumococcal surface protein A (PspA) is a virulence factor partially conserved among the Streptococcus pneumoniae isolates that plays a role in complement inactivation during infection (18). Based on amino acid sequence diversity, PspAs can be classified into three families and six clades (8) that also display immunological cross-reactivity among themselves (17). In several pneumoccocal infection challenge models, PspA has proved to be a good vaccine candidate when administered either in protein-adjuvant formulations or in DNA-based vaccines (4,11,12). PspA was also shown to bind and to prevent the bactericidal activity of apolactoferrin (15), present in saliva and other mucosal secretions. In addition, anti-PspA antibodies were shown to enhance pneumococcal killing by lactoferrin, suggesting a mechanism for the reduction of pneumococcal carriage by these antibodies (15). In a recent work, we tested the immunogenic potential of a fusion protein composed of the cholera toxin B subunit (CTB) and pneumococcal surface antigen A from Streptococcus pneumoniae by intranasal inoculation of mice (3). In this work, we have amplified the 5Ј terminus region (which encodes the ␣-helix region plus the prolinerich domain) of the pspA clade 3 gene from pTG-pspAЈ3 (11) (pspAЈ3 accession number, AY082389), which carried the gene isolated from S. pneumoniae St 259/98 strain (Instituto Adolpho Lutz, São Paulo, SP, Brazil). The pspAЈ gene was then cloned downstream of the ctxB gene in the pAE-CTB plasmid (2) in order to express a CTB-PspAЈ fusion protein in Escherichia coli. Using this expression system, the recombinant protein contains an N-terminal six-His tag that allows purification through Ni 2ϩ charged columns. This system was used for the expression and purification of the fusion protein CTB-PspAЈ and CTB, as previously described (2, 3), and PspAЈ, with the observation that the last protein did not adsorb very well, and it was released from the column with 20 mmol · liter Ϫ1 imidazole.Protein characterization. The recombinant CTB-PspAЈ purified from E. coli BL21-SI extracts was able to form pentamers, as evaluated by 6% sodium dodecyl sulfate-polyacrylamide gel electrophoresis of unboiled samples (data not shown). Since the adjuvant effect of CTB is dependent on the binding of the pentameric form to the GM1 gangliosides present on cellular surfaces (14), we performed an enzyme-linked immunosorbent assay (ELISA) experiment, using 10 g · ml Ϫ1 GM1 in phosphate-buffered saline for an overnight coating and incr...

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A mucosally administered recombinant fusion protein vaccine against schistosomiasis protecting against immunopathology and infection

Cited by 35 publications

References 33 publications

Current Status of Vaccines for Schistosomiasis

Current Status of Vaccines for Schistosomiasis

Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA

Intradermal Immunization of Mice with Cholera Toxin B-Pneumococcal Surface Protein A Fusion Protein Is Protective against Intraperitoneal Challenge with Streptococcus pneumoniae

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