Merck Animal Health (known as MSD Animal Health outside the USA and Canada) has signed an agreement with the Department of Medical Microbiology of the University Medical Center (UMC) Utrecht and the Faculty of Veterinary Medicine of Utrecht University to embark on the development of innovative vaccination strategies against bacterial udder infections (mastitis) in dairy cattle.

The project is titled “Evasion Molecules in Bovine Mastitis Vaccines” (EVAC) and its objective is to develop a series of vaccines against difficult to treat infections with certain bacteria known to cause bovine mastitis. Examples of such bacteria are Staphylococcus aureus, Streptococcus uberis and Escherichia coli. The EVAC project is part of the ALTANT (ALTernatives for ANTibiotics) program that is coordinated by Immuno Valley, a public-private research consortium. The program is funded by the Dutch Ministry of Economic Affairs, Agriculture & Innovation as well as by academic and industrial partners with the aim to generate knowledge and alternative tools that complement the available treatments to control infectious diseases in farm animals.

Dr Paul Vermeij, senior project leader at Merck Animal Health’s Discovery & Technology Department in Boxmeer (the Netherlands) explains: “In the open innovation model as applied in the EVAC project, we are combining the veterinary vaccine expertise of Merck Animal Health with the knowledge on evasion molecules of the Department of Medical Microbiology at UMC Utrecht and the expertise on bovine immunology available at the Faculty of Veterinary Medicine at Utrecht University.”

“The technologies developed within the ALTANT programme may result in an efficacious vaccine against bovine mastitis. In combination with our current therapeutic tools, it can result in unprecedented possibilities to control the disease. In addition to improvement of animal welfare and economic advantages for the farmer, such a vaccine can also contribute to a responsible use of antibiotics,” added Dr. Rene Aerts, vice-president Global Biologicals R&D at Merck Animal Health.

Development of vaccines against bovine mastitis has long been hampered due to the fact that the relevant pathogens are capable of producing so-called ‘immune evasion molecules’ that block or interfere with important processes in the immune system of the cow. Similarly, evasion molecules also appear to interfere with the immune response that is provoked with vaccines. Therefore, despite the induction of high antibody levels, the clinical efficacy of most mastitis vaccines that have been developed so far has been poor.

In the EVAC project, evasion molecules have been identified and characterized, and subsequently recombinant versions of these proteins have been produced. Combinations of such evasion molecules will be added to traditional antigens in candidate vaccines. Vaccination is expected to raise neutralizing antibodies against immune evasion molecules in the animal. As a consequence, the evasion system of the bacteria is impaired and the antibodies are able to neutralize the mastitis-causing pathogens. The availability of effective vaccines in addition to the current therapeutic treatments would provide unprecedented possibilities for the control of the disease and contribute to ongoing efforts to reduce the use of antibiotics.

Mastitis is a major problem for the dairy industry, affecting animal health and causing significant economic loss to the farmer of up to € 300 per cow per year (early culling, reduced milk yield, treatment costs and discarded milk). Although treatment with antibiotics is a common part of mastitis management, it is often associated with high treatment costs and its irresponsible use is increasingly associated with the risk of developing antibiotic resistance.

The ALTANT (ALTernatives for ANTibiotics) programme was started in 2008 by Immuno Valley, a Dutch public-private consortium of 27 partners from industry, academia and government. The program focuses on sustainable research on infectious diseases in human and animals and the development of alternatives for antibiotics. Initially, four projects were selected out of 12 submissions (ALTANT I) and the first phase, working on ‘proof of potential’, was initiated with support of the Dutch government of approx. US$ 3.2 million (€ 2.3 million). In 2011, the two most promising projects (“Evasion Molecules in Bovine Mastitis Vaccines” - EVAC and “Animal-Specific Immunomodulatory Antimicrobials” - ASIA) were selected for the second phase (ALTANT II) by an independent steering committee. ALTANT II is funded for a total of approx. US$ 25 million (€ 18 million) by the Dutch Ministry of Economic Affairs, Agriculture & Innovation, academic institutions and the industry partners in the programme (Merck Animal Health and Pfizer Animal Health).