Reproductive diseases in sheep and cattle pose significant economic challenges. Therefore, SEFARI researchers at the Moredun Research Institute, funded by the Scottish Government’s Strategic Research Programme, are pioneering the development of new vaccines to tackle these issues. In particular, our focus is on preventing abortions and stillbirths in sheep caused by Chlamydia abortus (enzootic abortion of ewes also known as ovine enzootic abortion or ovine chlamydiosis) and in cattle due to Neospora caninum (neosporosis). In this blog, we delve into the importance of these diseases for livestock producers, the need for innovative reproductive vaccines, and the strategies being employed to develop these vaccines.

 

Sheep on grass. (Source: Moredun communications archive)

Why are these diseases important to livestock producers?

Abortions and reproductive failures in sheep and cattle are a global problem. In the UK, the most common causes of infectious abortion in sheep and cattle, respectively, are Chlamydia abortus, a bacterium responsible for enzootic abortion in ewes and goats, and Neospora caninum, a parasite that primarily causes abortions in cattle and can also infect sheep, leading to neosporosis  (data collected by the Veterinary Investigation Diagnosis Analysis service).

Both organisms occur worldwide, with the notable exceptions of New Zealand and Australia for C. abortus, and both pathogens invade cells of the placenta, disrupting the nutrient and oxygen flow from the mother to the foetus, which ultimately results in the death of the foetus and abortion occurring.

The financial costs of C. abortus-induced abortions to the UK sheep industry have been estimated to be greater than £20 million per annum (according to Farmers Weekly), costing an estimated £2,163 per 100 ewes in Scottish sheep flocks. While the costs for foetal calf losses due to neosporosis in the UK have been estimated to be about £21 million each year. However, the costs for neosporosis do not include other associated costs, like reduction in milk yield; attempting to get cows pregnant again; maintaining non-pregnant/non-milking animals; and culling infected animals. Both infections also add significantly to the carbon footprint of livestock farming.

Why do we need novel reproductive vaccines?

There are two types of vaccine available to manage enzootic abortions of sheep in Europe and they are based on either inactivated or live (less pathogenic) strains of C. abortus. None of these vaccines are optimal due to limitations in terms of:

• safety (live vaccines can cause infections)
• stability (requiring a cold-chain for distribution and storage)
• shedding of infectious organisms from the animal (during and after lambing)
• or the short duration (1 year for inactivated vaccines) of protection from disease

Research at Moredun, has shown that the live vaccines can sometimes cause infection in animals, leading to disease and abortion in sheep but the bacteria in the vaccine can also pose a risk to pregnant women. There is also evidence that the live vaccine can be transmitted from infected to uninfected animals, resulting in the spread of infection to other animals within sheep flocks. Therefore, there is a clear need to develop cheaper, safer and more effective alternative vaccines that also produce a strong immune response in sheep that lasts over 2-3 years.

There are no licensed chemotherapeutics or vaccines available to treat bovine neosporosis. A previous vaccine (based on killed parasites) and only licensed in the USA was withdrawn from the market due to lack of efficacy as it did not actually prevent abortions or transmission.

How are we going to develop these new vaccines?

Both C. abortus and N. caninum are complex pathogens that live and multiply inside cells of infected animals, making it difficult for the host’s immune system to recognise and eliminate them. To control these pathogens inside cells, animals need to generate a very specific type of immune response, called a cell-mediated immune response, which is more challenging to achieve through standard vaccination. Therefore, such vaccines often consist of disabled pathogens or engineered viruses containing specific pathogen proteins that stimulate the appropriate immune response that recognises and kills these “hidden” pathogens without causing any infection or disease.

One of the main reasons why inactivated pathogen vaccines have not worked well for ovine chlamydiosis and neosporosis is that they are very poor at stimulating the required cell-mediated immune response. Therefore, we are developing vaccines, showcased also in our previous case study and publications, that will stimulate these cellular responses against both pathogens, which will be able to kill the pathogens even when they are hiding within cells.

For C. abortus, we are identifying bacterial proteins that are ‘seen’ by infected animals and that are good at stimulating these protective immune responses. Once we have confirmed which proteins work best, we will try two approaches to incorporate these proteins, or their genes into modified viruses to generate a vaccine that preferentially induces cellular immune responses as well as antibody-based responses, which together will lead to even better protection.

For N. caninum, we are opting for a disabled live vaccine. Previous work at Moredun, such as Protection against vertical transmission in bovine neosporosis and Immunity to experimental neosporosis in pregnant sheep, has shown that live parasites are better than killed/inactivated parasite vaccines at producing protective cell-mediated immune responses against neosporosis. However, if the parasite persists, then it could be transmitted in future pregnancies or cause abortions. The aim of the vaccine against neosporosis is to inactivate genes within the parasite that are essential for the parasite to persist. This ‘edited’ parasite will only be able to cause a transient infection, thereby stimulating cell-mediated immune responses, which protect against abortions due to future N. caninum infections.

Both proposed vaccines aim to generate cell-mediated immune responses in vaccinated animals that will protect them against future infections with either C. abortus or N. caninum. These vaccines will be highly desirable for sheep and cattle producers as they are either an improvement on the existing vaccines against enzootic abortions of ewes or the first vaccine that will protect cattle from abortions due to neosporosis.

Written by Dr Frank Katzer, Dr Sean Wattegedera, Dr Paul Bartley & Dr David Longbottom, Moredun Research Institute.