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Multivalent footrot vaccine developed by May 2018 – MLA

by Terry Sim, 16 July 2017

MLA managing director Richard Norton

MEAT and Livestock Australia hoped to have a cross-reactive footrot vaccine to protect against all serotypes of the crippling sheep condition in final development by May 2018, MLA managing director Richard Norton told breeders in Bendigo last night.

Speaking at the Australian Sheep Breeders Association dinner last night Mr Norton said a $1 million was being put toward development of the vaccine.

“A cross-reactive vaccine, one vaccine to protect sheep against all serotypes and again this is the sort of work that industry has demanded MLA do.

“We haven’t done a lot on footrot in the past – but over the last 12 months we’ve dedicated an enormous amount of our R&D back to industry to tell us where they want it spent.”

Sheep footrot is a debilitating and highly infectious disease caused by various strains of the bacteria Dichelobacter nodosus that affect the hooves of sheep and can lead to loss of body weight and reduced meat and wool production. Seasonal conditions in some states have increased the number of flocks affected, but current vaccines only treat specific serotypes within flocks.

A University of Sydney-led research team is due to complete the testing of antigens from the footrot bacterium which might protect sheep from infection by May 2018. Following that it will be a matter of turning one or more of those antigens into a vaccine, which then has to be tested and registered by the Australian Pesticides and Veterinary Medicines Authority before it can be sold, MLA said. It could take 5-7 years for a vaccine to be available to producers. The footrot research is levy-funded.

He said MLA was doing a lot of DNA work with footrot and Ovine Johne’s Disease on University of Sydney properties. The OJD research has not been funded by producer levy funds, but was coming from private and Federal Government investment.

“There are animals that one, don’t get Johne’s and two, when they get Johne’s, they recover.

“It’s about now having the ability to verify the DNA in this animals.

“We’re doing a lot of that work in footrot and Johne’s, with New Zealand, who also have a lot of data.”

He said footrot had devastated a lot of flocks from his home region, the Monaro, in New South Wales.

Mr Norton told the sheep breeders he appreciated animals must not be bred just for their carcase traits.

“It’s like flying a plane; there is no point being five metres off the ground doing 200 nautical miles an hour or something like that.

“You’ve got to have an animal that still gets in lamb, it still milks and that still survives in Australia’s environment.”

Clear and urgent need for multivalent footrot vaccine

University of Sydney in collaboration with Monash University has been working on development of a cross-protective footrot vaccine using reverse vaccinology since 2013.

According to a University of Sydney School of Veterinary Science project brief, there is no universal vaccine that is protective against all serotypes of footrot’s causative bacteria and there is a clear and urgent need for a multivalent footrot vaccine that protects sheep against all serogroups of D. nodosus.

Previous attempts to develop an effective footrot vaccine have focussed on the fimbriae produced by D.nodosus which are essential for virulence and are the major surface antigens. However, the university brief said there are ten major immunologically distinct fimbrial serogroups in D.nodosus and individual infections are often caused by more than one serogroup. These fimbriae are immunoprotective, but vaccination with a monovalent footrot vaccine will only protect against disease caused by isolates of the same serogroup. Multivalent fimbrial vaccines have been developed, but they are of limited value because of antigenic competition.

The university brief said reverse vaccinology is the process whereby complete genome sequence information is used to generate a list of potential vaccine candidates by use of bioinformatics tools. The genes encoding these candidates are then cloned, overexpressed and the resultant proteins tested for their ability to protect against disease. The advantages of this approach over more conventional methods that are used to identify vaccine candidates are that it allows the identification of a broader spectrum of antigens, including those that may be masked by immunodominant proteins, the university brief said. It also allows the analysis of all potential candidates from organisms that are more difficult to grow in laboratory conditions and it avoids any bias towards previously well-studied vaccine candidates.

Several years ago, University of Sydney researchers sequenced the genome of a virulent strain of D. nodosus and showed that this organism only carried 1299 potential genes.

“Subsequently, we decided to use this resource in a reverse vaccinology approach to identify genes encoding putative surface or secreted proteins that could be used to develop a multivalent vaccine against footrot.”

More recently the university has sequenced a further 85 strains from Australia, Norway, Denmark, UK, India, Bhutan and Nepal. These strains show remarkable sequence conservation, indicating that potential vaccine antigens are likely to be present in all D.nodosus isolates, the university said.

“From the complete D.nodosus genome, we identified 99 genes that were either secreted or surface located and therefore represented potential vaccine candidates.

“We have successfully cloned and overexpressed 89 of these proteins in Escherichia coli.”

The university said with the assistance of funding from Australian Wool Innovation, 63 of these recombinant proteins were tested in pen vaccination trials in sheep, which encouragingly showed that all of these proteins were capable of stimulating a specific antibody response.

“In addition, there are another 26 antigens that remain to be tested in sheep to determine if there are more protective antigens that could be used alone or in combination with the antigens already identified, to develop a multivalent footrot vaccine.”

The aim of this project is to complete the testing of these antigens in sheep and to determine which antigens, either alone or in combination, have potential for the development of an effective vaccine that could be used for the protection of sheep against footrot, the university brief said.

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