Roadmap for nematode vaccine development

Development of polyvalent vaccine giving long-lasting protection against the predominant nematode species infecting livestock. Protection can be defined as reducing pathology, production losses and/or pasture contamination.

• Multiple nematode species infecting host at same time.
• Variability in vaccine responses between hosts
• Interaction with other vaccines and/or treatments.
• Need for frequent boosting where hidden antigens are used.
• Identification of conserved protective antigens/epitopes across species and/or delivery of multiple antigens/epitopes.
• Parasites can modulate the host immune response.
• Immunological control of the different parasite species may require different branches of the immune response (e.g. systemic vs mucosal antibodies, humoral vs cell-mediated).
• An understanding of the host protective immune response and the antigens/epitopes that drive it.
• Recombinant expression of protective antigens/epitopes in the correct conformation.
• Several different antigens may be needed for each parasite species.
• The different antigens may interfere with each other e.g. enzymatic degradation/inhibition.

• Purification of sufficient native antigen(s) or expression of recombinant versions to allow for commercial scale-up.
• Slow release of purified antigens from an adjuvant that drives the immune response in the correct direction.
• Use of concatenated or co-expressed antigens/epitopes.
• Use of a replicating vector to reduce number of boosts.
• Nucleic acid-based vaccines based on self-amplifying RNA technology.
• A combination of different candidates (subunit/nucleic acid-based/vectored) in a prime-boost approach.
• Collation and analysis of all relevant trial data, both successful and otherwise

• A challenge model for species of interest.
• Definition of minimal acceptable efficacy.
• Identity of protective antigens.
• Definition of protective immune response required for each parasite species.
• Identity of suitable molecular adjuvants.
• Identity of delivery platform.
• Increase farmers’ intention to adopt vaccination against GIN, as well as/instead of routine anthelmintic treatment.

• PP2A (recombinant part of the catalytic region of the serine/threonine phosphatase 2A) from hookworms used as polyvalent vaccine in trials to protect lambs against mixed nematode infections. Questionable efficacy (Mohamed Fawzi et al., 2013)
• Cocktail vaccine of 8 antigens for Teladorsagia gives up to 70% reduction in FEC (Nisbet et al, 2013), simplification of vaccine cocktail required – Co-expression of multiple antigens to simplify production (Teladorsagia vaccine in PARAGONE) – vaccine lost efficacy
• Native (hidden) gut antigen vaccine Barbervax in commercial production, (Smith et al., Moredun), polyvalency not confirmed

Experimental vaccines against Ostertagia and Cooperia in cattle, based on purified native ASP antigens. Field efficacy confirmed for Cooperia vaccine (single experiment), not for Ostertagia. Recombinant expression of protective antigens unsuccessful so far.