The innate immune stimulant Amplimune® is safe to administer to young feedlot cattle

Abstract

Background Infectious disease has a significant impact on livestock production. Availability of alternatives to antibiotics to prevent and treat disease is required to reduce reliance on antibiotics while not impacting animal welfare. Innate immune stimulants, such as mycobacterium cell wall fractions (MCWF), are used as alternatives to antibiotics for the treatment and prevention of infectious disease in a number of species including cattle, horses and dogs. This study aimed to evaluate the safety of Amplimune®, an MCWF-based immune stimulant, for weaner Angus cattle.Methods On day À1 and 0, sixty mixed-sex Angus weaner cattle were transported for 6 h before being inducted and housed in a large single pen, simulating feedlot induction conditions. The cattle were assigned to one of six treatment groups (n = 10 per group): 2 mL Amplimune intramuscularly (2IM); 2 mL Amplimune subcutaneously (2SC); 5 mL Amplimune intramuscularly (5IM); 5 mL Amplimune subcutaneously (5SC); 5 mL saline intramuscularly (SalIM) and 5 mL saline subcutaneously (SalSC) on day 0 following transportation. Body temperature, body weight, concentrations of circulating pro-inflammatory cytokines (TNFα, IL-1β, IL-6 and IL-12) and haematology parameters were measured at various times up to 96 h post-treatment. ResultsNo adverse effects from Amplimune treatment were observed. Amplimune induced an increase in circulating cytokine TNFα concentrations, total white blood cell count and lymphocyte counts indicative of activation of the innate immune system without causing an excessive inflammatory response.Conclusions Results confirm that Amplimune can be safely administered to beef cattle at the dose rates and via the routes of administration investigated here.

Does the immune stimulant Amplimune® modulate humoral and cytokine responses to commercial bovine respiratory disease vaccines in cattle?

“…The absence of detectable negative effects on the immune responses to vaccination evaluated in the current study and safety data from prior experiments (Alexander et al 2022) support the further evaluation of the benefits of Amplimune in either experimental trials that include a pathogenchallenge component or in a commercial feedlot setting. The inclusion of a pathogen-challenge component to future pen trials would enable the indirect assessment of any benefits of Amplimune on the complete immune response to vaccination, rather than the limited number of immune factors measured in the current study.…”

“…The primary interest in using Amplimune is to potentiate nonspecific immune defences as an alternative to antibiotics for the prevention and/or treatment of microbial diseases, such as BRD, in production animals. In view of its previously noted adjuvant-like activities (Alexander et al 2022), administration of Amplimune might also confer beneficial or detrimental effects on antigen-specific responses of the adaptive immune system to contemporaneous vaccination. In the current study, Amplimune, administered at the same time, but at a different anatomical location, as Bovilis MH + IBR or Rhinogard in yearling beef cattle had no detrimental effect on responses to vaccination.…”

“…With the well accepted model of BRD development involving a predisposing viral infection (McGill and Sacco 2020), the use of adjuvants that elicit Th1 type responses may be preferred for prevention and treatment of BRD. Previously, subcutaneous injection of M. phlei cell-wall fractions in cattle has been shown to increase the production of the Th1 cytokine tumour necrosis-factor alpha in serum (Alexander et al 2022), but did not influence interleukin 12 (IL12), another cytokine typically associated with the Th1 response. Nonetheless, contemporaneous administration of innate immune stimulants with commercial vaccines may enhance, or indeed have undesirable effects on the immune response to commercial vaccines.…”

“…For example, the health and clinical signs in dairy calves suffering from enterotoxigenic Escherichia coli infection were significantly improved when calves were administered Amplimune (Romanowski et al 2017). The safety of Amplimune administered by subcutaneous or intramuscular injection, to cattle slightly younger and lighter than the typical age and weight class entering Australian feedlots was recently established (Alexander et al 2022). However, the effects of Amplimune on vaccine efficacy, when administered at the same time, but at a different site, as existing vaccine formulations on host immune responses in cattle remains unknown.…”

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“…The formulation of aluminium hydroxide, monophosphoryl lipid A, and fungal mannan, delivered subcutaneously, elicited rapid (24 h) and sustained (28 days) innate immune responses that protected mice from bacterial and fungal challenge [ 171 ]. Alexander et al [ 172 ] reported that a similar innate immune system stimulant, Amplimune ® , is safe for use in young beef cattle. Amplimune ® consists of the cell wall fractions of Mycobacterium phlei formulated with squalene.…”