WJ Enright

Intervet International BV, PO Box 31, 5830 AA Boxmeer, The Netherlands

The rationale for several decades of research into immunocontraception and immunocastration of farm, domestic and feral animals has been discussed extensively (see text box: Bonneau and Enright, 1995; Enright, 1995; Enright et al. 1995; Meloen, 1995; Becker et al. 1999; Delsink et al. 2002). If developed properly, active immunisation regimens can be cheap, practical and effective ways of generating effective antibody titres against a target molecule; however, the immune response can vary considerably between animals and a lag period is inevitable before the biological response is observed.

There are many factors other than inter-animal variation that determine the success of an active immunisation approach, including species, age, structure of the hormone/peptide, type of carrier molecule and adjuvant used, conjugation procedure, dose of antigen and adjuvant, molar ratio of hormone to carrier, and frequency and relative timing of immunisation (see Crowe et al. 1995).

(Dis)Advantages of bull beef production
Aggressive behaviour and libido can be a serious problem during the husbandry of male cattle. Post-pubertal bulls are difficult to handle, cannot be grazed near heifers, cause pasture damage and are a threat to human safety. These problems create management difficulties in all commercial beef systems, including grass-based extensive and intensive housing/feedlot systems. In addition, because of their high activity level, bulls have a greater tendency to yield bruised and dark-cutting meat at slaughter. To overcome these problems, in many countries male cattle are castrated using either the burdizzo or conventional surgical methods. However, while castration renders male cattle docile, it also decreases growth and feed conversion efficiency by 15%, and increases the fat content of the meat. The challenge is to therefore to reduce aggressive behaviour while maintaining the performance advantages of bulls. Immunisation against GnRH has proven a promising approach.

Immunisation of pre-pubertal bulls
In an initial study, Finnerty et al. (1994, 1996) immunised 47 three-month (mo) old Friesian bull calves against GnRH using various GnRH conjugate doses, adjuvants and booster intervals (1 or 2 mo post primary injection). Immunisation decreased LH and testosterone (T) secretion for 2 to 4 mo after the booster; thereafter, LH and T returned to levels approaching those of control bulls. Immunisation also decreased the incidence of aggressive and sexual behaviour at pasture, but had no effect on growth. In a follow-up study, Finnerty et al. (1997a, b) confirmed that GnRH immunisation prior to puberty (injections at 3 and 5, 3 and 7, 3 and 9, 3 and 11 or 3, 5, 7, 9 and 11 mo of age) transiently reduced T in all 50 animals (e.g. Figure 1) and reduced aggressive behaviour until slaughter at 21 mo of age (although not quite to the level of control steers). When a primary and a single booster were used (e.g. 5 and 7 mo group), growth was similar to that of control bulls and much superior to that of steers. Repeated immunisation (3, 5, 7, 9, 11 mo group) resulted in aggressive behaviour similar to that of steers for the duration of the study, including the last week (see Figure 2), while growth rate was similar to control bulls and considerably better than steers. Immunised bulls showed reduced homosexual behaviour at pasture at 9-12 mo of age, although there was no consistent effect at later ages.

Fig. 1

Fig. 2

In a similar study in New Zealand, Jago et al. (1997) looked at the effect of the timing of primary immunisation (as early as 2 mo of age, as late as 7.5 mo of age) and the number of booster immunisations. In all cases, immunisation delayed the prepubertal increase in T, and there was no difference in behaviour between the immunocastrate groups. From 10-17 mo of age, sexual behaviour of immunocastrates was intermediate between that of steers and bulls. Throughout the study aggressive behaviour was highest in bulls, while steers and immunocastrates were equal until 16 mo of age. Immediately prior to slaughter, at 18 mo of age, close monitoring during a 16 hr period of lairage revealed that steers now displayed much less sexual and aggressive behaviour, and that immunocastrates were only marginally less aggressive than bulls.

Immunisation of peri- and post-pubertal bulls
When 12-mo-old bulls were immunised against GnRH (Finnerty et al. 1995), T concentrations fell to at or near surgical castrate levels for the last 14 wk of a 20-wk study. During this time, sexual behaviour of the immunocastrates was also similar to that of surgical castrates while, compared to intact bulls, aggressive interactions were slightly reduced in duration but not frequency. Immunisation retarded growth to the same extent (≈25%) as surgical castration. In studies performed in California (Huxsoll et al. 1998; Price et al. 2003), bulls received a primary immunisation at 1, 4 or 6 mo of age and a booster at 12 mo. When observed at 16 mo of age, immunocastrates had aggressive behaviour similar to that of steers.

Conclusion
On the basis of the above studies, it is apparent that an optimised GnRH immunisation protocol for pre-pubertal bulls would be a viable option for obtaining the docile behaviour of steers but (close to) the growth rate of bulls. However, if GnRH immunisation is delayed until after puberty, growth rate is more likely to be adversely affected while the effects on behaviour may be inadequate. Furthermore, immunomodulation of endogenous hormone activity is an attractive alternative to other methods of increasing the efficiency of animal production because vaccine residues are not perceived by consumers to be a problem, and because the approach is conducive to good animal welfare.

Acknowledgements
The author would like to thank all former collaborators and students, especially JF Roche, M Crowe, M Finnerty and D Prendiville.

References
Becker SE, Enright WJ and Katz LS (1999) Active immunization against gonadotropin-releasing hormone in female white-tailed deer. Zoo Biology 18: 385-396.

Bonneau M, Enright WJ (1995) Immunocastration in cattle and pigs. Livest Prod Sci 42: 193-200.

Crowe MA, Enright WJ and Roche JF (1995) Immunisation of heifers against prostaglandin F2a. Livest Prod Sci 42: 213-221.

Delsink AK, van Altena JJ, Kirkpatrick J, Grobler D and Fayrer-Hosken RA (2002) Field applications of immuno-contraception in African elephants (Loxodonta africana). Reprod Suppl 60: 117-124.

Enright WJ (1995) Immunocastration of cats and dogs. Irish Vet Times, October, pp 43-47.

Enright WJ and Swift PJ. (1995) GnRH immunization of peripubertal male cats: dose titration of a GnRH-gly-cys-ovalbumin (GnRH-OVAL) conjugate on immune and testicular responses. J Reprod Fert Abstract Series No. 15: 15.

Finnerty M, Enright WJ, Morrison CA and Roche JF (1994) Immunization of bull calves with a GnRH analogue-human serum albumin conjugate: effect of conjugate dose, type of adjuvant and booster interval on immune, endocrine, testicular and growth responses. J Reprod Fert 101: 333-343.

Finnerty M, Enright WJ, Prendiville DJ, Spicer LJ, Crowe MA and Roche JF (1995) Immunisation of post-pubertal bulls against gonadotrophin-releasing hormone (GnRH): effect on hormones, behaviour and performance. Irish J Agric Food Res 34: 91-92.

Finnerty M, Enright WJ, Prendiville DJ, Spicer LJ and Roche JF (1996) The effect of different levels of gonadotropin-releasing hormone antibody titres on plasma hormone concentrations, sexual and aggressive behaviour, testis size and performance of bulls. Anim Sci 63: 51-63.

Finnerty M, Enright WJ, Harrington D and Roche JF (1992) Active immunisation against gonadotrophin-releasing hormone in bulls: antibody titres, testicular and body growth, sexual and aggressive behaviour and carcass characteristics. Irish J Agric Food Res 31: 97.

Finnerty M, Roche JF and Enright WJ (1997a) Immune response, testes function, body growth and carcass characteristics of bulls immunized against GnRH at 3 to 11 mo of age. J Anim Sci 75, Suppl 1: 213.

Finnerty M, Roche JF, Harrington D and Enright WJ (1997b) The effect of delaying the pubertal rise in plasma testosterone (T) on aggressive and homosexual behavior. J Anim Sci 75, Suppl. 1: 214.

Huxsoll CC, Price EO and Adams TE (1998) Testis function, carcass traits, and aggressive behavior of beef bulls actively immunised against gonadotropin-releasing hormone. J Anim Sci 76: 1760-1766.

Jago JG, Cox NR, Bass JJ and Matthews LR (1997) The effect of prepubertal immunization against gonadotropin-releasing hormone on the development of sexual and social behavior of bulls. J Anim Sci 75: 2609-2619.

Meloen RH (1995) Basic aspects of immunomodulation through active immunization. Livest Prod Sci 42: 135-145.

Price EO, Adams TE, Huxsoll CC and Borgwardt RE (2003) Aggressive behavior is reduced in bulls actively immunised against gonadotropin-releasing hormone. J Anim Sci 81: 411-415.