Elsevier

Vaccine

Volume 33, Issue 43, 26 October 2015, Pages 5861-5867
Vaccine

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

https://doi.org/10.1016/j.vaccine.2015.07.110Get rights and content
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Highlights

  • High partial protection against murine filariasis by O. volvulus GAPDH vaccine.

  • Two formulations produced significance: DNA vaccine and DNA/rProtein vaccine.

  • L. sigmodontis adult worm count and microfilariae were reduced by 57% and 94%.

  • In prepatency, pDNA-immunized mice had higher Ov-GAPDH-reactive Ig levels.

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.

Graphical abstract

BALB/c mouse pictures used in the graphical abstract were taken from the website of Taconic Biosciences: http://www.taconic.com/balb. The schematic picture of a human being as well as the subcutaneous Onchocerca volvulus nodule and the picture of the Onchocerca volvulus adult worms used in the depiction of the principle of cross-immunization, can be found on the WHO website: http://www.who.int/apoc/onchocerciasis/lifecycle/en/http://www.who.int/apoc/media/adult_worms.JPG. The picture of Litomosoides sigmodontis L3 can be found on the website of the University of Tübingen: http://www.oncholab-sokode.de/forsch.htm. Syringe pictures were purchased from: http://www.dreamstime.com/vvostal_info#res11064437. The Litomosoides sigmodontis microfilariae and adult worms symbolizing the parasitic readout of the experiments were drawn in the style of the CDC Onchocerca volvulus life cycle: http://www.cdc.gov/dpdx/images/onchocerciasis/O_volvulus_LifeCycle.gif.

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Abbreviations

Mf
microfilaria(e)
OvE
Onchocerca volvulus somatic extract
LsE
Litomosoides sigmodontis somatic extract
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
PBS
phosphate buffered saline
ELISA
enzme-linked immunosorbent assay
Ig
immunoglobulin(s)
PI
putative immune individual

Keywords

O. volvulus
L. sigmodontis
Glyceraldehyde-3-phosphate dehydrogenase
Protective potential
DNA vaccine
Moonlighting proteins

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