A reverse vaccinology approach to developing a vaccine for bovine trichomoniasis
Lead Research Organisation:
University of Liverpool
Department Name: Institute of Infection and Global Health
Abstract
Tritrichomonas foetus is a single-celled protozoan parasite that causes the venereal disease bovine trichomoniasis in cattle. This disease is found worldwide, including Europe and North America and is a potential threat to the UK cattle industries. Bovine trichomoniasis can cause infertility in bulls, and increases rates of spontaneous abortion and foetal maceration in cows. Thus, there are considerable economic effects, reducing calving rates by up to 35% and causing many infected animals to be culled. Currently there is no vaccine available that can provide long-lasting immunity and prevent reinfection.
This project aims to identify candidates for a bovine trichomoniasis vaccine using a reverse vaccinology approach, by producing an annotated T. foetus genome sequence and evaluating all possible antigen genes found within it for their immunogenic potential.
A T. foetus genome will be sequenced on the PacBio platform and annotated using gene predictive software in conjunction with transcriptomic and proteomic data. Potential vaccine candidates will be identified from antigen proteins that fulfil several criteria: they will be i) parasite-specific; ii) cell-surface expressed; iii) naturally immunogenic; iv) consistently expressed; and v) structurally invariant across the parasite population.
To evaluate these criteria we will: i) compare T. foetus genes containing structural motifs that predict surface expression with other parasites; ii) validate putative cell-surface expression using protein localization assays and cell-surface proteomics; iii) identify known antibody epitopes in target gene sequences and screen parasite peptide microarrays with infected bovine serum; iv) quantify antigen gene expression using transcriptomic assays in vivo; and v) quantify structural variation in antigen genes by re-sequencing parasite DNA isolated from natural infections.
This project will produce validated vaccine candidates as a first step in producing a viable vaccine against bovine trichomoniasis, facilitating clinical trials into the efficacy of vaccination as an effective strategy to eradicate the disease.
This project aims to identify candidates for a bovine trichomoniasis vaccine using a reverse vaccinology approach, by producing an annotated T. foetus genome sequence and evaluating all possible antigen genes found within it for their immunogenic potential.
A T. foetus genome will be sequenced on the PacBio platform and annotated using gene predictive software in conjunction with transcriptomic and proteomic data. Potential vaccine candidates will be identified from antigen proteins that fulfil several criteria: they will be i) parasite-specific; ii) cell-surface expressed; iii) naturally immunogenic; iv) consistently expressed; and v) structurally invariant across the parasite population.
To evaluate these criteria we will: i) compare T. foetus genes containing structural motifs that predict surface expression with other parasites; ii) validate putative cell-surface expression using protein localization assays and cell-surface proteomics; iii) identify known antibody epitopes in target gene sequences and screen parasite peptide microarrays with infected bovine serum; iv) quantify antigen gene expression using transcriptomic assays in vivo; and v) quantify structural variation in antigen genes by re-sequencing parasite DNA isolated from natural infections.
This project will produce validated vaccine candidates as a first step in producing a viable vaccine against bovine trichomoniasis, facilitating clinical trials into the efficacy of vaccination as an effective strategy to eradicate the disease.
Organisations
People |
ORCID iD |
| Andrew Jackson (Primary Supervisor) | |
| Eleanor Senior (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011186/1 | 01/10/2015 | 31/03/2024 | |||
| 1797320 | Studentship | BB/M011186/1 | 01/10/2016 | 31/12/2020 | Eleanor Senior |