Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

Abstract

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunization protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans.

Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite Onchocerca volvulus and Its Wolbachia Endosymbiont

“…While their exact role in O. volvulus is not clear, the expression of polyglutamine repeats was shown to be neurotoxic in both C. elegans and Drosophila and is dynamically regulated throughout the lifetime of an organism, suggesting a link to longevity (15). Interestingly, one of the lead O. volvulus vaccine candidates (16), Ov-RAL-2 (OVOC9988), has 11 glutamine residues in its amino terminus. These residues are probably not important for the protective ability of this protein, as the Brugia malayi homologue (Bm2001), that is also protective in animals, does not have this repeat (17).…”

Factors affecting onchocerciasis transmission: lessons for infection control

“…Based on successful results using animal models, some candidate vaccines against onchocerciasis have been found [105,106] and further trials are planned. The potential deployment of a vaccine has been modelled and it was concluded that after 15 years of a childhood vaccination programme it would have a protective effect and be valuable for preventing re-emergence of the disease in areas cleared of the infection [107].…”

Linear epitopes in Onchocerca volvulus vaccine candidate proteins and excretory‐secretory proteins

“…Based on a mouse‐ Onchocerca model, the top ranking eight Ov protective antigens ( Ov ‐CPI‐2, Ov ‐ALT‐1, Ov ‐RAL‐2, Ov ‐ASP‐1, Ov ‐103, Ov ‐RBP‐1, Ov ‐CHI‐1, and Ov ‐B20) were chosen for more extensive studies . Using two model systems, O. volvulu in mice and Brugia malayi in gerbils, this list of candidates has been reduced to the final selection of Ov ‐103 and Ov ‐RAL‐2 for further clinical development …”