Sheep Milk Smart Antigens

Biotech innovators Ruakura Technologies (RuaTech) are working with University of Waikato scientists to develop sheep milk with enhanced immune protection against norovirus – and they’ve already proved the concept with the Covid-19 virus. 

In 2020, at the start of the pandemic, the government funded COVID-19 Innovation Acceleration Fund was set up to accelerate innovative solutions and responses to COVID-19, and to develop and more quickly deploy a range of new products, services, and processes. A group of like-minded scientists began thinking about what they could contribute. University of Waikato Applied Immunologist William Kelton and Biochemist Adele Williamson had been working with Ruakura Technologies (RuaTech), a biotechnology company based just off campus, when the call came for ideas. 

RuaTech Chief Executive Officer Grant Smolenski explains they wanted something outside of developing tests for the SARS-CoV-2 virus, “We’re all molecular biologists and immunologists and we knew we had something to offer in this space.” 

Aware of the risk of public transmission within communities, the group looked to ways to reduce transmission. “The hyperimmune milk concept had been around for a while but we were confident we had an edge to better leverage it, using modern technology,” says Grant. 

Members of the RuaTech team had previous experience in developing ‘hyperimmune milk’ – enabling animals to produce antibodies in their milk to aid human health. Taken as a nutraceutical or health supplement, the aim is to reduce the effects of infection and improve recovery time. 

The science of hyperimmune milk mimics nature and can be compared to the way a mother’s milk protects a newborn baby. In essence any milk-producing animal, when triggered by a pathogen, will produces antibodies, some of which pass into the milk and provide protection to the offspring. 

The point of difference the team bought to the table was developing a “smart antigen” to produce antibodies that not only targets the way viruses infect the cells but lasts longer to generate more specific antibodies. 

The initial trials of this technology were performed on sheep, as they were easier to handle than cattle and available on-site at Ruakura. Sheep were also chosen because the Waikato region has a developing sheep milking industry with a strong interest in developing innovative new value-added products. 

The process begins with the development of artificial components to mimic the outer protein or antigen of the virus of interest. The antigen is important because this is what the host’s body will recognise and use to mount an immune response against the invader. 

William Kelton and Adele Williamson worked closely to engineer an artificial ‘smart antigen’. 

Adele Williamson looks at the structure of a virus of interest to make decisions about how to design the antigen. She explains, “We do not need to engineer an entire structure, we need to streamline the design so that only the components that are going to trigger a desired response are included.”  

William Kelton is charged with developing the parts of the antigen that directly enhance antibody producing immune responses. These engineered proteins are species-specific and are joined directly to the antigen for delivery, providing a short cut for immune activation. They’ve labelled the resulting structure, a ‘smart-antigen’. 

This ‘smart-antigen’ is administered to sheep to stimulate an immune response so the sheep then naturally produces antibodies in its milk, notably in its colostrum. Antibodies are produced by the body to neutralise invading viruses. Hyperimmune milk can then be used as a supplement to bolster humans against a specific disease-causing virus.  

In a trial conducted in 2022 (with results published in 2023) the team achieved a proof of concept with sheep producing hyperimmune milk that specifically targeted the COVID-19 virus. “One thing we’ve learned from Covid-19 is that the ability to provide early interventions when vaccines and medicines are still being developed is really important” says Dr Kelton.  

“Vaccination remains our gold standard for preventing viral illness but hyperimmune products offer a valuable and rapid solution when vaccines are still under development or facing challenges from emerging viral mutations.” 

Off the back of this proof of concept, the team are now working with funds from an MBIE Endeavour Grant, to produce a hyperimmune milk for norovirus. 

Norovirus is a gastro-intestinal virus, and outbreaks are well known for rapidly moving through densely populated settings like age-care facilities, early childhood centres and cruise ships. There are no effective treatments and people simply must suffer through a few days of vomiting, diarrhoea and stomach pain – while remaining highly infectious. 

Every year norovirus causes around 685 million infections worldwide and is estimated to cost $60 billion dollars in lost productivity – with people off work sick or caring for others. With few treatment options currently available, the global market for a health product to boost protection is huge. 

“Imagine the benefits of being able to supply large quantities of bioactive antibodies to help people to avoid or fight off viral infection during outbreaks of common viruses in a rest home or an early childcare centre – or at the start of a future viral pandemic?” says Dr Kelton. 

Grant explains that the end product will not be available in bottled milk at the supermarket but be delivered in a dried milk powder to be made as a flavoured drink.  

It is envisaged the additive will also be used in a range of health products that can be bought to market. RuaTech are currently working with other companies to explore product possibilities.  

The team are also working to increase the effectiveness of the hyperimmune milk by increasing the numbers of antibodies specific to any virus of interest. There are different types of antibodies, and they want to bias the milk to produce those that specifically function in the parts of the human body associated with the disease. For example, in the case of norovirus they are targeting the numbers of IgA antibodies as these work best in the human gastro-intestinal tract. 

They’re also looking to how they can develop the technology for use across different ruminant species.  

Hyperimmune milk research is accelerating value-add technologies to maximise the economic potential of our agriculture sector. Of interest to farmers will be the estimated value of a hyperimmune milk. It will be many times the standard milk-solid prices with early modelling suggesting only a few weeks of hyperimmune milk production could enable farmers to significantly reduce herd size – or even halve their herd – without reducing income.