Harnessing the Power of the Innate Immune System to Protect Livestock Against Disease

Abstract

<p>Innate immune stimulants, particularly those that can trigger trained immunity and influence the adaptive immune response, have potential as antibiotic alternatives, especially for use in livestock industries. Trained immunity is the ability of the innate immune response to develop epigenetic and metabolic shifts, which allow rapid responses to subsequent challenges, and influence the direction of the adaptive immune response. This ability has potential for use by livestock managers, to induce specific rapid immunity in livestock.</p> <p>Bovine respiratory disease has negative health and economic consequences for the cattle feedlot industry in Australia. Vaccines are used to prevent infection by some pathogens associated with the disease, and antibiotics are used to treat the disease once identified, but absolute protection is not afforded to every animal. Innate immune stimulants may have an important role to play in enhancing immunity against a range of pathogens associated with the disease and if trained immunity is triggered, may be able to shape the adaptive immune response, enhancing overall immune strength.</p> <p>Amplimune is an innate immune stimulant containing fractions of cell walls of the non-pathogenic <i>Mycobacterium phlei</i>. Research has been conducted in Canada and America, administering Amplimune to calves and dairy cows but similar studies have not been executed in Australia. Hence the aim of this thesis was to test the safety of Amplimune when administered to Australian cattle and to investigate the mechanism of action on bovine immune responses. Further aims were to explore whether concurrent administration of Amplimune, with commercial vaccines against bovine respiratory disease, would enhance adaptive immune responses to those vaccines and to define the transcriptional response of bovine immune cells to <i>in vitro </i>stimulation with Amplimune.</p> <p>The summation of this thesis was that Amplimune was proven safe when administered to cattle, the pro-inflammatory effect of Amplimune on <i>ex vivo</i> and <i>in vitro </i>bovine immune cells was illuminated, and we identified that Amplimune was associated with a Th1/Th17 type response which was potentially indicative of trained immunity. The mechanistic and transcriptomic studies on Amplimune are the first of their kind, adding significantly to the body of knowledge on the effect of Amplimune on bovine immune cells in vitro. Moreover, this thesis has clarified the potency of Amplimune in modulating the cytokine profile, hence shaping the adaptive immune response. The results of experiments in this thesis are important for the progression of approval for the use of Amplimune in the Australian cattle industry.</p>