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

A. L. Alexander; E. K. Doyle; A. B. Ingham; I. G. Colditz; N. M. Andronicos; B. C. Hine; T. J. Mahony

doi:10.1071/AN23235

RESEARCH ARTICLE (Open Access)

Next Contents Vol 64(4)

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

A. L. Alexander

^A ^B ^* , E. K. Doyle

^A , A. B. Ingham

^C , I. G. Colditz

^B , N. M. Andronicos

^A , B. C. Hine

^B and T. J. Mahony

^D

+ Author Affiliations

- Author Affiliations

^A Faculty of Science, Agriculture, Business and Law, University of New England, Armidale, NSW 2350, Australia.

^B CSIRO Agriculture and Food, F.D. McMaster Laboratory, New England Highway, Armidale, NSW 2350, Australia.

^C CSIRO Agriculture and Food, Queensland Biosciences Precinct, 306 Carmody Road, St Lucia, QLD 4067, Australia.

^D Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4067, Australia.

^* Correspondence to: aalexa25@une.edu.au

Handling Editor: Andrew Fisher

Animal Production Science 64, AN23235 https://doi.org/10.1071/AN23235

Submitted: 30 June 2023 Accepted: 30 January 2024 Published: 23 February 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

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 non-specific 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 cells in 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.

Keywords: Amplimune, cattle, enhanced immunity, inactivated vaccine, innate immune stimulant, modified live vaccine, mycobacterial cell wall fractions, respiratory disease.

References

Alexander AL, Doyle E, Ingham AB, Colditz I, McRae G, Alkemade S, Cervantes MP, Hine BC (2022) The innate immune stimulant Amplimune® is safe to administer to young feedlot cattle. Australian Veterinary Journal 100, 261-270.
| Crossref | Google Scholar | PubMed |

Alexander A, Ingham A, Colditz I, Hine B, Doyle E, Alexandre P (2023) AMR mission fund Amplimune in feedlots. CSIRO Data Access Portal, CSIRO.

Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang S-Y, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG (2018) BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host & Microbe 23, 89-100.e5.
| Crossref | Google Scholar | PubMed |

Blakebrough-Hall C, McMeniman JP, González LA (2020) An evaluation of the economic effects of bovine respiratory disease on animal performance, carcass traits, and economic outcomes in feedlot cattle defined using four BRD diagnosis methods. Journal of Animal Science 98, skaa005.
| Crossref | Google Scholar |

Blecha F (2000) Immune system response to stress. In ‘The biology of animal stress’. (Eds GP Moberg, JA Mench) pp. 111–122. (CAB International: Oxford, UK)

Broderson RJ (1989) A retrospective review of lesions associated with the use of Freund’s adjuvant. Laboratory Animal Science 39, 400-405.
| Google Scholar | PubMed |

Chandran A, Williams K, Mendum T, Stewart G, Clark S, Zadi S, Lanni F, McLeod N, Williams A, Villarreal-Ramos B, Vordermeier M, Maroudam V, Prasad A, Bharti N, Banerjee R, Manjari Kasibhatla S, McFadden J (2019) Development of a diagnostic compatible BCG vaccine against bovine tuberculosis. Scientific Reports 9, 17791.
| Crossref | Google Scholar |

Chowdhury SI, Wei H, Weiss M, Pannhorst K, Paulsen DB (2014) A triple gene mutant of BoHV-1 administered intranasally is significantly more efficacious than a BoHV-1 glycoprotein E-deleted virus against a virulent BoHV-1 challenge. Vaccine 32, 4909-4915.
| Crossref | Google Scholar | PubMed |

Cusack PMV, McMeniman N, Lean IJ (2003) The medicine and epidemiology of bovine respiratory disease in feedlots. Australian Veterinary Journal 81, 480-487.
| Crossref | Google Scholar | PubMed |

de Souza KA, Cooke RF, Schubach KM, Brandão AP, Schumaher TF, Prado IN, Marques RS, Bohnert DW (2018) Performance, health and physiological responses of newly weaned feedlot cattle supplemented with feed-grade antibiotics or alternative feed ingredients. Animal 12, 2521-2528.
| Crossref | Google Scholar | PubMed |

Ertl HCJ (2003) Viral Immunology. In ‘Fundamental Immunology’, 5th edn, (Ed. WE Paul) pp. 1201–1223. (Lippincott Williams & Wilkins)

Filion MC, Lépicier P, Morales A, Phillips NC (1999) Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells. British Journal of Cancer 79, 229-235.
| Crossref | Google Scholar | PubMed |

Fox J, Weisberg S (2019) ‘An (R) companion to applied regression.’ (Sage Publishing: Thousand Oaks, CA, USA)

Fulton RW, Confer AW, Burge LJ, Perino LJ, d’Offay JM, Payton ME, Mock RE (1995) Antibody responses by cattle after vaccination with commercial viral vaccines containing bovine herpesvirus-1, bovine viral diarrhea virus, parainfluenza-3 virus, and bovine respiratory syncytial virus immunogens and subsequent revaccination at day 140. Vaccine 13, 725-733.
| Crossref | Google Scholar | PubMed |

Gaughan JB, Sullivan ML (2014) Australian feedlot industry. In ‘Beef cattle production and trade’. (Eds L Kahn, D Cottle) pp. 314–358. (CSIRO Publishing: Melbourne, Vic., Australia)

Gill HS, Altmann K, Cross ML, Husband AJ (2000) Induction of T helper 1- and T helper 2-type immune responses during Haemonchus contortus infection in sheep. Immunology 99, 458-463.
| Crossref | Google Scholar | PubMed |

Griebel P (1999) Evaluation of the ability of MCWF immunostimulant to alter blood leucocyte populations in newborn calves. Vaccine and Infectious Disease Organisation Experiment Report for Vetrepharm Research Inc. Available at http://novavive.ca/bovine-research [accessed 3 February 2019]

Haak T, Delverdier M, Amardeilh MF, Oswald IP, Toutain PL (1996) Pathologic study of an experimental canine arthritis induced with complete Freund’s adjuvant. Clinical and Experimental Rheumatology 14, 633-641.
| Google Scholar | PubMed |

Hay KE, Barnes TS, Morton JM, Clements ACA, Mahony TJ (2014) Risk factors for bovine respiratory disease in Australian feedlot cattle: use of a causal diagram-informed approach to estimate effects of animal mixing and movements before feedlot entry. Preventive Veterinary Medicine 117, 160-169.
| Crossref | Google Scholar | PubMed |

Hay KE, Morton JM, Mahony TJ, Clements ACA, Barnes TS (2016) Associations between animal characteristic and environmental risk factors and bovine respiratory disease in Australian feedlot cattle. Preventive Veterinary Medicine 125, 66-74.
| Crossref | Google Scholar | PubMed |

Hill K, Arsic N, Nordstrom S, Griebel PJ (2019) Immune memory induced by intranasal vaccination with a modified-live viral vaccine delivered to colostrum fed neonatal calves. Vaccine 37, 7455-7462.
| Crossref | Google Scholar | PubMed |

Hodgson PD, Aich P, Stookey J, Popowych Y, Potter A, Babiuk L, Griebel PJ (2012) Stress significantly increases mortality following a secondary bacterial respiratory infection. Veterinary Research 43, 21.
| Crossref | Google Scholar | PubMed |

Hurley DJ, Barber CE, Adkins M, Rowson AD, Norton NA, Nickerson SC, Ely LO, Kautz FM, McLean DJ, Chapman JD (2019) An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers. Research in Veterinary Science 127, 11-17.
| Crossref | Google Scholar | PubMed |

Kubota M, Iizasa E, Chuuma Y, Kiyohara H, Hara H, Yoshida H (2020) Adjuvant activity of Mycobacteria-derived mycolic acids. Heliyon 6, e04064.
| Crossref | Google Scholar | PubMed |

Lenth R (2020) emmeans: estimated marginal means, aka least-squares means. R package version 1.5.2-1.

McGill JL, Sacco RE (2020) The immunology of bovine respiratory disease: recent advancements. Veterinary Clinics of North America: Food Animal Practice 36(2), 333-348.
| Crossref | Google Scholar |

Murphy K, Weaver C (Eds) (2017) ‘Janeway’s immunobiology.’ (Garland Science/Taylor Francis Group: New York, NY, USA)

Nosky BJ, Biwer J, Alkemade S, Prunic B, Milovanovic A, Maletic M, Masic A (2017) Effect of a non-specific immune stimulant (Amplimune™) on the health and production of light feedlot calves. Journal of Dairy, Veterinary & Animal Research 6, 302-306.
| Crossref | Google Scholar |

Novak B, Vatzia E, Springler A, Pierron A, Gerner W, Reisinger N, Hessenberger S, Schatzmayr G, Mayer E (2018) Bovine peripheral blood mononuclear cells are more sensitive to deoxynivalenol than those derived from poultry and swine. Toxins 10, 152.
| Crossref | Google Scholar | PubMed |

Omontese BO, Caixeta LS, Machado VS, Rendahl A, Celestino MLK, Menta PR, Paiva D, Garcia-Munoz A, Masic A (2020) Effects of the administration of a non-specific immune stimulant around transportation on health and performance of Jersey and Jersey-cross heifer calves during the rearing period: randomized clinical trial. Frontiers in Veterinary Science 7, 550202.
| Crossref | Google Scholar |

Osman R, Gonzalez-Cano P, Brownlie R, Griebel PJ (2017) Induction of interferon and interferon-induced antiviral effector genes following a primary bovine herpesvirus-1 (BHV-1) respiratory infection. Journal of General Virology 98, 1831-1842.
| Crossref | Google Scholar | PubMed |

O’Callaghan A, Kuhn M, Weston S, Wing J, Forester J, Thaler T (2020) contrast: a collection of contrast methods. R package version 0.22.

Pinheiro J, Bates D, DebRoy S, Sarkar D, R Core Team (2020) nlme: linear and nonlinear mixed effects models. R package version 3.1-150.

Purswani S, Talwar GP, Vohra R, Pal R, Panda AK, Lohiya NK, Gupta JC (2011) Mycobacterium indicus pranii is a potent immunomodulator for a recombinant vaccine against human chorionic gonadotropin. Journal of Reproductive Immunology 91, 24-30.
| Crossref | Google Scholar | PubMed |

R-Core-Team (2018) ‘R: a language and environment for statistical computing.’ (R Foundation for Statistical Computing: Vienna, Austria)

Romanowski R, Culbert R, Alkemade S, Medellin-Peña MJ, Bugarski D, Milovanovic A, Nesic S, Masic A (2017) Mycobacterium cell wall fraction immunostimulant (AMPLIMUNE™) efficacy in the reduction of the severity of ETEC induced diarrhea in neonatal calves. Acta Veterinaria 67, 222-237.
| Crossref | Google Scholar |

Stils HF, Jr. (2005) Adjuvants and antibody production: dispelling the myths associated with Freund’s complete and other adjuvants. ILAR Journal 46, 280-293.
| Crossref | Google Scholar |

Taylor JD, Fulton RW, Lehenbauer TW, Step DL, Confer AW (2010) The epidemiology of bovine respiratory disease: what is the evidence for predisposing factors? The Canadian Veterinary Journal = La Revue Veterinaire Canadienne 51, 1095-1102.
| Google Scholar | PubMed |

Wheat W, Chow L, Rozo V, Herman J, Still Brooks K, Colbath A, Hunter R, Dow S (2020) Non-specific protection from respiratory tract infections in cattle generated by intranasal administration of an innate immune stimulant. PLoS ONE 15, e0235422.
| Crossref | Google Scholar | PubMed |

Woolums AR, Siger L, Johnson S, Gallo G, Conlon J (2003) Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production. Vaccine 21, 1158-1164.
| Crossref | Google Scholar | PubMed |

Zimmermann P, Curtis N (2018) The influence of BCG on vaccine responses – a systematic review. Expert Review of Vaccines 17, 547-554.
| Crossref | Google Scholar | PubMed |

Zimmermann P, Donath S, Perrett KP, Messina NL, Ritz N, Netea MG, Flanagan KL, van der Klis FRM, Curtis N (2019) The influence of neonatal Bacille Calmette-Guérin (BCG) immunisation on heterologous vaccine responses in infants. Vaccine 37, 3735-3744.
| Crossref | Google Scholar | PubMed |