Novel Immunotherapy For Brucellosis And Biomarker-Based Assessment Of Antimicrobials Could Save Animal Lives And Prevent Economic Losses

Brucellosis caused by Brucella organisms takes a heavy toll on the farm economy due to abortions and reproductive failure in farm animals like cattle, buffaloes, goats, sheep, pigs, etc. The disease leads to other painful conditions like arthritis, mastitis, etc. Presently, there is no satisfactory treatment for this dreadful disease, as antibiotics are not effective and prolonged treatment is uneconomic. Once infected, the animal remains a carrier for the rest of its life.

The disease is endemic in a large number of countries and continues to spread despite vaccination with the Brucella abortus S19 live attenuated strain vaccine. In India alone, the annual losses due to Brucellosis are estimated to be around 2.86 billion US dollars. Unfortunately, due to social, religious, and political reasons, cow slaughter is banned in India; hence, Brucellosis-affected cows cannot be slaughtered in this country.

A novel immunotherapy developed by Dr. Hari Mohan Saxena, a Professor of Immunology at Guru Angad Dev Veterinary and Animal Sciences University (GADVASU), Ludhiana in India, has been shown to eliminate live B. abortus organisms from Brucellosis infected adult cattle in 3 months with a single subcutaneous injection of 2 ml dose of the bacterial lysate (phage killed bacteria). The efficacy of the antibacterial therapy was monitored non-invasively for the first time from the blood plasma of the treated animals, employing a biomarker specific to the B. abortus organisms. Hitherto, a destructive method was practiced worldwide for evaluating the in vivo effect of anti-bacterials. In this inhumane method, the antibiotic-treated infected animals were killed, the organs were harvested, and single cell suspensions of the tissues were made for determining the bacterial counts which were compared with the counts in the untreated infected animals.

H M Saxena and Sugandha Raj at the cow shed. Image courtesy H M Saxena.

The new non-invasive method could save a huge amount of money, time, and lives of millions of experimental animals who are killed mercilessly to determine the in vivo efficacy of new antibacterial therapies and vaccines. Thus, new antibiotics, antibacterial therapies, and vaccines can be developed in a shorter amount of time, with less money, and in a safer way.

Dr. Saxena and his team used lysates of two attenuated strains of B. abortus organisms, S19 and RB51, killed with a lytic bacteriophage (a virus that specifically kills particular bacteria) as an immunotherapy for Brucellosis in cattle. The S19 lysate stimulates the production of anti-Brucella antibodies, while the RB51 lysate enhances the cell-mediated immunity against the Brucella organisms. The resultant immune response is adequate to kill the virulent Brucella organisms in the animal.

The new findings have been published in PLOS Neglected Tropical Diseases. Dr. Saxena has also delivered an invited keynote address on his research at an international conference in Zurich, Switzerland. The innovations have far-reaching implications since the same principles of immunotherapy and biomarker-based monitoring of therapy can also be applied to a large number of other bacterial diseases of animals and humans like Tuberculosis, Salmonellosis, etc. Dr. Saxena’s team included his MVSc students Dr. Sugandha Raj and Dr. Vimlesh Gupta, who worked with him on immunotherapy trials and phage isolation, respectively.