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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

2019
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.

2018
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.

2017
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 years 4-5 the work will focus on testing the efficacy of prototype vaccines against a range of parasites (worms which live in the stomach of sheep and cattle; liver fluke; sheep scab mites) under experimental conditions and, in some cases, in the field. Further testing of a vaccine to protect sheep against one of the major bacterial causes of mastitis will also be carried out and the outcomes of the optimisation experiment for the vaccine to control enzootic will be analysed with a view to pushing the vaccine towards commercialisation. Efforts will also be made to make the Barbervax vaccine commercially available in the UK. New ways to deliver vaccines will be assessed by adapting animal viruses to optimise their expression of antigens from a range of pathogens will continue to be developed and their ability to stimulate protective immune responses against the relevant pathogens will be assessed.

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.

Research Deliverable Lead