Roadmap for nematode vaccine development

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Identity of protective antigens

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Identity of protective antigens

Research Question

To identify antigens against which protective immune responses could be generated.
The parasite must utilise gene products which allow it to establish, feed and evade host responses – can these be used as immunogens?
Alternatively, there may be factors which could be targeted such as (hidden) parasite gut antigens not recognised by the host immune system during the course of a natural infection.

Lack of fully annotated genomes on which to base reverse vaccinology approaches to antigen identification.
Size of predicted transcriptome/proteome from which to select antigens.
What is the basis of putative antigen selection from large genomic/transcriptomic/proteomic datasets?
Generation of genetically modified parasites lacking “virulence” factors or immunomodulators, or application of RNAi technology in parasites
Extensive genetic polymorphism in parasite populations, what are the implications for antigenic variation and vaccine development?

Establish the identity and role of putative “virulence” factors and immunomodulators by generating genetically modified parasites or blocking them using RNAi technology.
Identify subsets of proteins on which to focus reverse vaccinology approaches.
Use convalescent/immune sera to identify antigens by immunoprecipitation or immunoscreening.
Establish which parasite genes are being expressed at different stages of the parasites’ life-cycles and identify those involved in vital biological processes e.g. feeding, tissue migration

Good genome sequencing and annotation.
Improved understanding of the mechanisms of protection against the various parasite species e.g. antibody classes vs cell-mediated immunity.
Identity of parasite-derived virulence factors or factors needed for feeding.
Identity of immunomodulators.
Reliable RNAi technology for all nematode species

A native microsomal aminopeptidase (H11) and a galactose-containing glycoprotein complex form the main components of the native H. contortus Barbervax vaccine
Vaccination of cattle with native activation-associated secreted proteins (ASP) of O. ostertagi and C. oncophora gave a significant reduction in faecal egg count
Rational approach used to identify the 8 antigens in the Teladorsagia vaccine through understanding immunomodulation and immunodominance.
Reverse Vaccinology for helminths (schistosomes, de Souza et al., 2018)
General comment that vaccine ‘failures’ are rarely, if ever, published.