Towards a recombinant antigen vaccine against Onchocerca volvulus

Lustigman, Sara; James, Eric R.; Tawe, Wilson; Abraham, David

doi:10.1016/s1471-4922(01)02211-5

Cited by 77 publications

(54 citation statements)

References 54 publications

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“…This evidence indicates the unique immunological characteristics of irradiated L 3 and strongly supports the feasibility of immunoprophylaxis against Onchocerca spp. However, because irradiated L 3 could never be used in humans because of constraints on mass production, stability, and safety, the next step is to reproduce significant protection using defined antigens (47).…”

Section: Discussionmentioning

confidence: 99%

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Tchakouté

Graham

Jensen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than agematched, naïve controls (P ‫؍‬ 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P ‫؍‬ 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P ‫؍‬ 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host-Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions. filariasis ͉ irradiation ͉ larvae ͉ ochengi ͉ Onchocerca

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Section: Discussionmentioning

confidence: 99%

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Tchakouté

Graham

Jensen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Currently, one larval antigen is being evaluated in a phase 1 clinical trial in a region of Brazil that is endemic for hookworm and a second adult hookworm antigen is about to enter into clinical trials (170). Related antigens are also being used to develop recombinant onchocerciasis vaccines (171). In addition, the Institut Pasteur is conducting clinical trials in sub-Saharan Africa using a recombinant vaccine (encoding a glutathione S-transferase) to protect against infection with S. haematobium (172).…”

Section: Global Control Of Helminthiases and Clinical Research Imperamentioning

confidence: 99%

Helminth infections: the great neglected tropical diseases

et al. 2008

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Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

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“…Recombinant antigen vaccines against helminth infections have been tested with limited success (8,28,35,36), which in part may be due to the altered conformation and/or glycosylation of the recombinant antigens. An alternative vaccination approach has been to immunize mice with DNA, where the protein product is produced in vivo from the plasmid DNA.…”

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confidence: 99%

DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

et al. 2005

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Strongyloides stercoralis causes chronic asymptomatic infections which can be maintained in the human host for many decades. Identification and treatment of S. stercoralis-infected individuals is required because immunosuppression can lead to fatal hyperinfection. In this study, human immunoglobulin G (IgG) that had previously been shown to transfer protective immunity to mice was used to identify potential protective antigens. Three antigens or genes from S. stercoralis larvae were identified as tropomyosin (Sstmy-1), Na ؉ -K ؉ ATPase (Sseat-6), and LEC-5 (Sslec-5). The genes were cloned into plasmids for DNA immunization, and mice were immunized intradermally with the three plasmids individually in combination with a plasmid containing murine granulocyte-macrophage colony-stimulating factor. Only Na ؉ -K

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Towards a recombinant antigen vaccine against Onchocerca volvulus

Cited by 77 publications

References 54 publications

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Helminth infections: the great neglected tropical diseases

DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

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Towards a recombinant antigen vaccine against Onchocerca volvulus

Cited by 77 publications

References 54 publications

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Helminth infections: the great neglected tropical diseases

DNA Immunization with Na + -K + ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

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Product

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DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice