Context. Feedlot entry can be a period of stress for cattle due to transportation, altered diets and other influences. Stress can suppress host defence mechanisms. Innate immune stimulants, such as mycobacterial cell-wall fractions, attract attention for the primary objective of enhancing nonspecific immune resistance of cattle against microbial diseases during periods of stress-induced susceptibility. These stimulants are also recognised for their capacity to modify responses of the adaptive immune system to vaccines. Aims. This study aims to evaluate the potential for mycobacterial cell-wall fractions in Amplimune® to modify adaptive immune responses to the commercial vaccines Rhinogard® (modified live bovine alphaherpesvirus-1 (BoHV-1)) and Bovilis MH + IBR® (inactivated Mannheimia haemolytica and BoHV-1) in yearling cattle during simulated feedlot induction. Methods. Fifty-four mixed-sex Angus yearling cattle were transported for 6 h on Day −1 and on Day 0. The cattle were assigned to the following six treatment groups (n = 9/group): Rhinogard plus 2 mL Amplimune, Rhinogard plus 5 mL Amplimune, Bovilis MH + IBR plus 2 mL Amplimune, Bovilis MH + IBR plus 5 mL Amplimune, Rhinogard plus 5 mL saline, and Bovilis MH + IBR plus 5 mL saline. Blood and nasal secretions were sampled at various time points following treatment and antigen-specific antibody (immunoglobulin G) responses to components of the vaccines were assessed. Interferon-γ production by peripheral blood mononuclear cellsin response to BoHV-1, Concanavalin A or media only were assessed. Key results. No adverse clinical reactions were observed to administration of Amplimune and vaccines. A systemic antibody response to vaccination was observed for the Bovilis MH + IBR vaccine. Vaccine-specific antibody and cytokine responses were not modified by Amplimune. Conclusions. Amplimune can be administered at the same time as Rhinogard or Bovilis MH + IBR vaccines, without undesirable effects on specific immune responses to vaccination. Implications. The primary interest in using Amplimune is to potentiate non-specific immune defences as an alternative to antibiotics for the prevention and/or treatment of microbial diseases such as bovine respiratory disease in production animals. In view of its adjuvant-like activities, administration of Amplimune might also confer beneficial or detrimental effects on antigen-specific responses of the adaptive immune system to contemporaneous vaccination.