Roadmap for nematode vaccine development

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Vectored vaccines

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Development of a vectored vaccine

Research Question

Using a replicating organism to give enhanced exposure to protective antigens and optimal delivery to the correct arm of the host’s immune system.
Attempting to avoid issues (folding/conformation/post-translational modifications) of recombinant protein-based vaccines

If the same organism (vector) is to express the protective antigens of several parasites it may need to have a relatively large genome.
Production of complex antigens from multicellular organisms.
That the expressed antigen has the correct conformation.
That revaccination doesn’t result in rapid elimination of the vector.
That an appropriate vector is available for the livestock species being immunised.
That the chosen vector stimulates the correct arm(s) of the immune response.
Regulatory and consumer issues regarding GMOs.
Potential pathogenicity/reversion of vector.

Development of a range of genetically modified organisms expressing protective antigens of one or more parasite species, either as a secreted entity or as a surface molecule.
Epitope mapping of antigens to reduce the complexity and size of the inserted genes for expression.

Identity of a suitable vector (e.g. Trypanosoma theileri or autologous retrovirus).
Identity of protective antigens and their genetic sequences.
Identity of correct protective immune response.

Adenovirus and canary pox virus widely used as vectors for other pathogens.
Eimeria system in hens (Tomley et al) – some success (Pastor-Fernández et al 2018 IJP 48, 505-518
Trypanosoma system (Matthews et al., 2016) – not yet proven