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Vaccines

Roadmap for nematode vaccine development

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Identity of protective antigens

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Dependencies

Next steps

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.

Research Gaps and Challenges

  • 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?

Solution Routes

  • 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

Dependencies

  • 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

State Of the Art

  • 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.

Projects

What activities are planned or underway?

Improving the performance of forage legumes through the use of optimal symbiotic partners using the example of sainfoin (Onobrychis viciifolia)

Planned Completion date 31/12/2023

Source Countries:

DenmarkIconDenmark

Development of a web application for the risk assessment of the worm load of free-range laying hens (Wurmfrei)

Planned Completion date 31/12/2026

Source Countries:

DenmarkIconDenmark