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Novel Vaccines

Work Package 2.2 - Livestock production, health and welfare

Research Deliverable 
2.2.5 Novel vaccines
Leading Ideas 
Agriculture
Plant and Animal Health

Introduction

Controlling endemic diseases of livestock in Scotland has major economic, environmental and animal health and welfare benefits for the nation. Vaccination against disease is recognised as being one of the most cost-effective and successful disease control strategies that can be implemented in both human and animal health. In selecting the livestock diseases to target for vaccine development in this work, we have taken into account the views of key stakeholders and have sought opinion directly from farmers and producers on disease prioritisation in Scottish livestock. Scottish Government policy priority areas have also informed this work, specifically through the key priority areas identified in the Scottish Rural Development Programme (SRDP) 2014-2020. The outcomes of the research performed here will align directly with key policy documents such as Scottish Government’s Animal Health and Welfare Strategy, Good Food Nation and Ambition 2030.

Aim of Research

The aim of this RD is to develop safe, highly effective, optimised, novel vaccines for the control of the most production- and welfare-limiting endemic diseases of Scottish livestock. The key drivers for this research are:

  • Prevention is better than cure.  Anthelmintics (chemotherapeutics for the control of intestinal worms) and antibiotics are used to treat diseases but can leave environmental residues, adversely affect operator and food safety and are not sustainable due to increasing resistance;
  • Vaccines offer a cost-effective, sustainable alternative to overcome these limitations and to provide increased productivity and efficiency in livestock production with economic, food security and environmental benefits, including reductions in greenhouse gas emissions.

Progress

2020 / 2021
2020 / 2021

As in many areas of the Strategic Research Programme, some of the studies planned on Novel Vaccines in Year 5 were impacted by the restrictions on travel and working imposed due to the COVID-19 pandemic. Nevertheless, progress was made in a number of areas: Using a complex vaccine against the “brown stomach worm” of sheep, in field experiments, showed that the vaccine demonstrated some level of protection in ewes around the time of lambing but that additional parasite species should be targeted for maximum impact in this setting. One of the highlights in Year 5 was, therefore, the discovery of components for incorporation into such a vaccine which may protect sheep against multiple species of parasitic worm.  A selection of regions in the brown stomach worm vaccine proteins have also been identified for further vaccine simplification and enhancement. These regions were selected using two independent computer-based techniques to identify which parts of the vaccine components are actually targeted by sheep antibodies. The results will allow us to further reduce the complexity of this vaccine. Vaccine trials to test a new prototype vaccine against parasitic worms which live in the abomasum (true stomach) of cattle also showed promising results and further work in this area will continue in Yr6. The prototype sheep scab vaccine was also assessed for long term storage of it’s components in different formats and best practise for long-term storage and preparation of the vaccine was established. In year 5, the use of animal viruses (“vectors”) to deliver vaccines against diseases of livestock was further progressed; key developments included enhancing the production efficiency of the vector system to produce more vaccine but also to incorporate further vaccine components to give protection against a range of livestock diseases. These updated methods will be used in future studies to produce vaccine for protection trials.

2019 / 2020
2019 / 2020

One of the highlights of work in this year was the progress in the use of animal viruses (“vectors”) to deliver vaccines against livestock diseases; key developments included the demonstration of strong immune responses against vaccines designed in this way following both initial and “booster” vaccinations. The vaccines being developed here encompass tick-borne and reproductive diseases of sheep and cattle respiratory diseases.  This work may lead to the production of new vaccines against the virus which causes louping ill (in sheep), for example, for which our stakeholders have expressed great interest.

Other work on novel delivery methods included the use of new technologies to deliver vaccines on the surface of microscopic “nanoparticles” and this work also showed that the components of a prototype sheep scab vaccine could be delivered to animals in this way and induce strong immune reactions. Work on the prototype sheep scab vaccine also demonstrated the ability to produce a diagnostic blood test which could discriminate between animals which were vaccinated and animals which were infected. This tool is a key component in the development of the vaccine if it is to be used in conjunction with effective diagnosis.  Further progress was also made with a vaccine to protect sheep against one of the major bacterial causes of mastitis, where it was demonstrated that the vaccine effect demonstrated in Yr3 was repeatable and gave some protection against two of the three major bacteria which cause mastitis. Work to demonstrate the effectiveness of a simplified prototype vaccine against the “brown stomach worm” of sheep, in field experiments, showed that the vaccine demonstrated low levels of protection in this setting so ewes in the second year of the experiment (Y4) were vaccinated with a more complex version of the vaccine while work continued to develop a vaccine which would protect sheep against multiple species of parasitic worm.  Vaccine trials to test a new prototype vaccine against parasitic worms which live in the abomasum (true stomach) of cattle showed promising results and further work in this area will continue in Yr5.

2018 / 2019
2018 / 2019

A clear highlight of this work in Year 3 was the authorisation for the sale of the Barbervax vaccine (which was developed by our scientists to control barber’s pole worm in the intestinal tract of sheep) under a Special Treatment Certificate in the UK. A different prototype simplified vaccine against another nematode, the “brown stomach worm” which lives in the abomasum of sheep was produced in large quantities to test it’s ability to prevent pregnant ewes contaminating the pasture with nematode eggs around the time of lambing. The vaccine was delivered safely with no adverse reactions.  Vaccine trials to test a new prototype vaccine against the nematodes which live in the abomasum of cattle and a refined version of another vaccine for the parasite, liver fluke, only provided low levels of protection, suggesting further optimisation will be needed. Progress was also made with a vaccine to protect sheep against one of the major bacterial causes of mastitis, where it was demonstrated that the vaccine effect was relatively short-lived, warranting further investigation into the specificity and duration of the response. For the prototype vaccine which was designed against sheep scab mites a trial was successfully completed to compare the vaccine produced in plants with the same vaccine made in our standard systems. Growth conditions in the lab for Chlamydia abortus, the major cause of abortion in sheep,  were further optimised and a novel vaccine was formulated in different adjuvants; two of these vaccine formulations gave high levels of protection against abortion and could be correlated with the type of immune response the vaccines generated. The use of animal viruses (“vectors”) to deliver vaccines against diseases of livestock was further progressed; key developments included the doubling of vaccine production by modifying the vector and demonstrating good immune responses against vaccines designed in this way. Ultimately this may lead initially to the production of a new vaccine against the virus which causes louping ill (in sheep) for which our stakeholders have expressed great interest.. Vaccines for other diseases could also exploit the same vectors.

2017 / 2018
2017 / 2018

The prototype simplified vaccine against nematodes which live in the abomasum of sheep was successfully tested in 6 month old lambs and gave acceptable levels of protection and the liver fluke vaccine which was based on extracts of the flukes also reduced the numbers of parasites in vaccinated sheep by approximately 50%. For the prototype vaccines which were designed against sheep scab mites and cattle gut nematodes, sufficient quantities of synthetic antigens were prepared in plants and bacteria (respectively) for future vaccine trials and appropriate methods for testing the effectiveness of the vaccines were also designed. Encouraging progress was also made with a vaccine to protect sheep against one of the major bacterial causes of mastitis, with full protection of all immunised sheep in a preliminary trial. Growth conditions in the lab for C. abortus were further optimised and the novel vaccine was formulated in different adjuvants to optimise protection. Immune responses to these differently formulated vaccines were analysed and will be used in Yr3 to determine how they relate to protection. Two further types of animal viruses were adapted to optimise their expression of antigens from a range of pathogens to help in their commercial production potential and effectiveness. A key example of this is our efforts to produce a novel louping ill vaccine for which there is a current market opportunity. One of our vaccines, against nematodes which live in the abomasum of sheep, was reformulated in a novel slow-release formulation to test for enhanced duration of immunity.

2016 / 2017
2016 / 2017

The research has focussed on two major aspects of vaccine development: designing prototype vaccines and optimising delivery systems for these vaccines to make them work to their full capacity. To address the first of these aspects, teams identified genetic information from parasitic worms (nematodes) which live in the stomach (abomasum) of sheep and cattle to allow them to produce synthetic versions of the worm proteins for use in future vaccination/protection experiments.  We typically use bacteria to produce these synthetic proteins in the laboratory, but one of our teams has started to use plants as a way of producing the synthetic proteins and has produced the proteins required for a prototype sheep scab vaccine in this system.  Staying with parasites, scientists in this RD made extracts of liver flukes and analysed the contents of these extracts to produce a prototype vaccine for testing in subsequent years of the programme.  Our groups working on vaccines against bacterial diseases optimised the growth conditions for Chlamydia abortus (which causes enzootic abortion in sheep) and extracted components from it to produce a vaccine. They tested the ability of various doses of this vaccine to protect sheep against abortion and showed that, even at a very low dose, the vaccine was effective. Importantly, they were also able to demonstrate that the vaccine could stimulate strong immune responses which can be used in future work to predict the effectiveness of vaccines. The second aspect of the work in this RD addresses vaccine delivery: Here the proteins from the pathogens (viruses, bacteria or parasites) which stimulate the protective immune responses can be delivered by injecting them with a compound which provokes the immune system (an adjuvant) or as part of a modified virus. Our scientists delivered anti-parasite vaccines in different adjuvants to try to stimulate long-lasting effects in sheep and our teams of virologists also created modified versions of a viral vaccine which allows the virus from the vaccine to be grown in large scale and to carry antigens from other infectious agents.

Future Activities

In year 6 the work will focus on testing the effectiveness of animal virus vectored vaccines against livestock diseases caused by a range of pathogens, under experimental conditions. Analysis of an experiment using different vaccine components to stimulate different elements of the sheep immune system against a prototype vaccine to protect against brown stomach worm will also be completed and the development of a vaccine to help control multiple species of parasitic worms in sheep will be continued. The ability to leverage external funding using these data will also be explored, The relative contributions of each of the components of a vaccine to protect sheep against one of the major bacterial causes of mastitis will also be carried out. Further development of a prototype vaccine to control parasitic worms which live in the abomasum (true stomach) of cattle will be under way and the further testing of an optimised formulation of a vaccine to protect sheep against sheep scab mite infestation will also be undertaken.

Selected Outputs

Immunity to Haemonchus contortus and Vaccine Development.

Protection of ewes against Teladorsagia circumcincta infection in the periparturient period by vaccination with recombinant antigens.

A recombinant subunit vaccine for the control of ovine psoroptic mange (sheep scab).

Niche-specific gene expression in a parasitic nematode; increased expression of immunomodulators in Teladorsagia circumcincta larvae derived from host mucosa.

A field vaccine trial in Tanzania demonstrates partial protection against malignant catarrhal fever in cattle.

Immune development and performance characteristics of Romney sheep selected for either resistance or resilience to gastrointestinal nematodes.

Global food security via efficient livestock production: targeting poor animal husbandry.

Genomic evidence that the live Chlamydia abortus vaccine strain 1B is not attenuated and has the potential to cause disease.

Enhancing the toolbox to study IL-17A in cattle and sheep.

Mind the gaps in research on the control of gastrointestinal nematodes of farmed ruminants and pigs

Estimating genetic and phenotypic parameters of cellular immune-associated traits in dairy cows.

Gene silencing by RNA interference in the ectoparasitic mite, Psoroptes ovis.

Draft Genome Assembly of the Sheep Scab Mite, Psoroptes ovis.

Presentations by Prof Gary Entrican and Dr. Alasdair Nisbet at the International Veterinary Vaccinology meeting

Presentations at the International Veterinary Vaccinology meeting: Vaccines projects at Moredun Research Institute

Presentations at the International Veterinary Vaccinology meeting: A successful vaccine trial reveals an opportunity to control Malignant Catarrhal Fever in cattle.

The rational simplification of a recombinant cocktail vaccine to control the parasitic nematode Teladorsagia circumcincta.

Immunological Homeostasis at the Ovine Placenta May Reflect the Degree of Maternal Fetal Interaction

Abortion storm induced by the live C. abortus vaccine 1B strain in a vaccinated sheep flock, mimicking a natural wild-type infection.

Trials with the Haemonchus vaccine, Barbervax®, in ewes and lambs in a tropical environment: Nutrient supplementation improves protection in periparturient ewes.

Presentations at the World Vaccines Congress: Exploration and design of novel vaccination strategies for parasites of livestock

The Potential for Vaccines Against Scour Worms of Small Ruminants

Senescence in Immunity Against Helminth Parasites Predicts Adult Mortality in a Wild Mammal

Proteomic Characterisation of the Chlamydia abortus Outer Membrane Complex (COMC) Using Combined Rapid Monolithic Column Liquid Chromatography and Fast MS/MS Scanning

A Novel Technique for Retrospective Genetic Analysis of the Response to Vaccination or Infection Using Cell-Free DNA From Archived Sheep Serum and Plasma

A Genomic Analysis and Transcriptomic Atlas of Gene Expression in Psoroptes Ovis Reveals Feeding- And Stage-Specific Patterns of Allergen Expression

Duration of Protection and Humoral Immunity Induced by an Adenovirus-Vectored Subunit Vaccine for Foot-And-Mouth Disease (FMD) in Holstein Steers

https://www.frontiersin.org/articles/10.3389/fvets.2020.00036/full


 

 

The potential for vaccines against scour worms of small ruminants

Helminths, hosts, and their microbiota: new avenues for managing gastrointestinal helminthiases in ruminants

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

The 1B vaccine strain of Chlamydia abortus produces placental pathology indistinguishable from a wild type infection

Attempts to induce tolerance to Trichostrongylus colubriformis infection in sheep

Intramammary Immunisation Provides Short Term Protection Against Mannheimia haemolytica Mastitis in Sheep

Defining immune correlates during latent and active chlamydial infection in sheep

Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant

Moredun’s Centenary Science Stories Volume 1: Enzootic Abortion of Ewes 

Prevention and control of ovine abortion: Test don’t guess