title: DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) leads to partial protection in a mouse model of human filariasis.
abstract: River blindness, caused by the filarial parasite Onchocerca volvulus, is a major socio-economic and public health problem in Sub-Saharan Africa. In January 2015, The Onchocerciasis Vaccine for Africa (TOVA) Initiative has been launched with the aim of providing new tools to complement mass drug administration (MDA) of ivermectin, thereby promoting elimination of onchocerciasis in Africa. In this context we here present Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) as a possible DNA vaccine candidate. We report that in a laboratory model for filariasis, immunization with Ov-GAPDH led to a significant reduction of adult worm load and microfilaraemia in BALB/c mice after challenge infection with the filarial parasite Litomosoides sigmodontis. Mice were either vaccinated with Ov-GAPDH.DNA plasmid (Ov-pGAPDH.DNA) alone or in combination with recombinantly expressed Ov-GAPDH protein (Ov-rGAPDH). During the following challenge infection of immunized and control mice with L. sigmodontis, those formulations which included the DNA plasmid, led to a significant reduction of adult worm loads (up to 57% median reduction) and microfilaraemia (up to 94% reduction) in immunized animals. In a further experiment, immunization with a mixture of four overlapping, synthetic Ov-GAPDH peptides (Ov-GAPDHpept), with alum as adjuvant, did not significantly reduce worm loads. Our results indicate that DNA vaccination with Ov-GAPDH has protective potential against filarial challenge infection in the mouse model. This suggests a transfer of the approach into the cattle Onchocerca ochengi model, where it is possible to investigate the effects of this vaccination in the context of a natural host-parasite relationship.
authors: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.
authors: Vera
authors: V
authors: Steisslinger
authors: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany; Department of Infection Medicine, Laboratory Lademannbogen Medical Service Center GmbH (Sonic Healthcare Group), Lademannbogen 61-63, D-22339 Hamburg, Germany.
authors: Simone
authors: S
authors: Korten
authors: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.
authors: Norbert W
authors: NW
authors: Brattig
authors: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany. Electronic address: Erttmann@bni-hamburg.de.
authors: Klaus D
authors: KD
authors: Erttmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D005368:Filariasis / Q000517:prevention & control*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D017181:Onchocerca volvulus / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D059208:Parasite Load; D010957:Plasmids / Q000008:administration & dosage; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D004337:Drug Carriers; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: DNA vaccine; Glyceraldehyde-3-phosphate dehydrogenase; L. sigmodontis; Moonlighting proteins; O. volvulus; Protective potential