Development and use of recombinant gonadotropin-releasing Development and use of recombinant gonadotropin-releasing hormone vaccines to sterilize cattle: a review hormone vaccines to sterilize cattle: a review

A possible alternative to conventional castration methods is the use of vaccines that can be injected in order to sterilize animals. One promising approach involves the use of a vaccine that causes cattle to produce an immune response against one of their own reproductive hormones, gonadotropin releasing hormone (GnRH). Immunization against GnRH results in a decrease in the amount of GnRH circulating within the animal's blood. Therefore, follicle stimulating hormone (FSH) and luteinizing hormone (LH) are not stimulated to be released, and, subsequently their levels required for reproductive function. Experimentation has shown that immunization against GnRH can effectively block reproductive function in an age-independent manner but has little effect on carcass and growth parameters. However, about 10% of cattle tested do not respond when immunized against GnRH, regardless of dosing regimen. Further research is needed to improve the efficiency of potential GnRH immunocastration vaccines.; Dairy Day, 1997, Kansas State University, Manhattan, KS, 1997;


Summary
The amino acid sequence of GnRH is com-A possible alternative to conventional castra-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH .In tion methods is the use of vaccines that can be theory, immunizing an animal against GnRH injected in order to sterilize animals.One prom-would elicit endogenous production of antiising approach involves the use of a vaccine that GnRH antibodies within the animal's body.causes cattle to produce an immune response These antibodies then would recognize and neuagainst one of their own reproductive hormones, tralize endogenously produced GnRH.Immunigonadotropin releasing hormone (GnRH).
zation of cattle against GnRH would result in Immunization against GnRH results in a decrease decreased releases of LH and FSH, which, in in the amount of GnRH circulating within the turn, would inhibit both testicular and ovarian animal's blood.Therefore, follicle stimulating development and function.hormone (FSH) and luteinizing hormone (LH) are not stimulated to be released, and, subse-Immunization Effects in Heifers quently, their levels within the body fall below the levels required for reproductive function.
Active immunization of postpubertal beef Experimentation has shown that immunization heifers, using a vaccine in which GnRH was against GnRH can effectively block reproductive conjugated to ovalbumin in complete Freund's function in an age-independent manner but has adjuvant (CFA), was found to induce antibodies little effect on carcass and growth parameters.
against GnRH at a level that could be detected in However, about 10% of cattle tested do not the serum.These same heifers also were found respond when immunized against GnRH, regard-to have retarded follicular growth, with most less of dosing regimen.Further research is ovaries showing no developing follicles.Pregneeded to improve the efficiency of potential nancy tests were negative for all immunized GnRH immunocastration vaccines.heifers (n=7) at the time of slaughter following (Key Words: Gonadotropin Releasing Hormone, animals had a pregnancy rate of 71%.Further Follicle Stimulating Hormone, Luteinizing studies found that active immunization of heifers Hormone, Antibody, Immunization.)against similar GnRH constructs resulted in de-

Introduction within the pituitary, concentrations of LH within
Gonadotropin releasing hormone (GnRH) is weight, uterine weight, follicular development, a neuropeptide synthesized by neurons in the and cyclic activity.Multiple immunization of hypothalamus of the brain.GnRH travels to the cyclic beef heifers with GnRH conjugated to anterior pituitary via the hypothalamic-hypophy-human serum albumin (HSA) and injected in seal portal system, where it triggers subsequent diethylaminoethyl (DEAE)-dextran adjuvant not releases of FSH and LH.Released into general only invoked and maintained anti-GnRH titers, circulation, FSH and LH travel to the gonads, but also induced a state of anestrus in 29 of 34 where they regulate steroid production, folliculo-heifers for 82.8 ± 6.9 days.This effect was not genesis in the ovary, and spermatogenesis in the dependent on the dose of vaccine.testis.mon to all mammalian species; pyro-Glu-His-2 an 8-week breeding period.In contrast, control creases in: the number of receptors for GnRH the pituitary, serum progesterone levels, ovarian Research has shown that immunization of Immunization of prepubertal heifers against GnRH can delay the Steers and Bulls onset of puberty.In 12-month-old heifers receiving two injections of GnRH-HSA in CFA 6 Both single-and double-dose administration weeks apart, puberty was delayed by an average of a vaccine consisting of GnRH conjugated to of 175 days.A single immunization delayed the keyhole limpet hemocyanin (KLH) induced longonset of puberty by an average of 112 days.Pre-lasting, high levels of anti-GnRH antibodies.In sumably, these delays were due to decreases in these animals, LH concentrations in the serum the secretion of LH and FSH, which ordinarily were decreased, and immunized bulls also had stimulate development of the ovaries at the time retarded testicular growth and decreased of puberty.
epididymal weight.Immunization also elicited A potential concern about the use of steril-prostate and seminal vesicles.ization vaccines is that the immunization ultimately may cause a decline in the release of Immunization against GnRH did not affect certain growth-promoting (anabolic) steroids.
the average daily gain in bulls and steers to the Multiple studies have demonstrated that GnRH-extent seen in heifers, and carcass characteristics immunization treatments reduced average daily of the immunized animals were comparable to gain (ADG) in feedlot heifers but did not affect those of control individuals.Immunization overall carcass quality.This decreased growth effects also were not dependent on age.performance likely was due to reduced estradiol secretions from acyclic ovaries in GnRH-immu-Considerations for nized individuals.This theory is supported by Vaccine Production early research showing ovariectomized heifers as generally having reduced ADG rates.We should In both bulls and heifers, one problematic note, however, that reductions in ADG in both aspect of vaccination against GnRH is the failure pre-and postpubertal heifers immunized against of some treated animals to respond to treat-GnRH can be overcome by the use of estradiol ment-overall about 10% of all injected animals implants.Additionally, these losses in ADG are failed to respond to GnRH immunization less than those seen when heifers become preg-whether given one or two injections.Additionnant in the feedlot.
ally, research has shown that, in order to main-A commercial anti-GnRH vaccine, sary in at least part of the cattle population.Vaxtrate®, is currently in use in Australia.
Success rate is dependent on several factors, Vaxtrate is a GnRH-ovalbumin conjugate admin-including vaccine construct and adjuvant.Curistered in a DEAE-dextran and mineral oil rent research at Kansas State University is examadjuvant.This vaccine is used primarily to ining the efficiency of various construct/adjuvant prevent pregnancy in feedlot cows and heifers at combinations as well as investigating the potentimes when pregnancy is of biological and eco-tial use of an "immunological cocktail", which nomical disadvantage (pregnant animals gener-would elicit an immunological response against ally gaining less and bringing a lower price per GnRH, LH, and FSH.The aim of these studies pound at slaughter).Cattle usually are dosed is to create an efficient, permanent vaccine for twice at an interval of 4 or 16 weeks.Currently, use in both male and female cattle, as well as producers using Vaxtrate® are seeing an 80% satisfying the previously mentioned FDA redecline in the incidence of pregnancy among quirements for vaccines used in food animals.vaccinated animals.Unfortunately, Vaxtrate® is One of these requirements is that the vaccine not available in the United States because of must have an easily identifiable structure that is restrictions placed on vaccine production by the perfectly consistent from batch to batch.Current Food and Drug Administration (FDA).
conjugation techniques (such as those used to atrophy of secondary sex organs, including the tain castration status, repeated dosage is neces-produce Vaxtrate®) do not meet these criteria.Conclusions Therefore, we are utilizing recombinant DNA techniques to produce vaccines against GnRH Development of a reliable, permanent, that will evoke an immune response, as well as immunological, castration vaccine has obvious have an identifiable structure (by reading the economical and ethical advantages.Castration DNA sequence of the construct) that is consis-via injection would reduce veterinary costs and tent from batch to batch.man-hours spent castrating and treating domestic livestock species--this is particularly true for the females who are not so easily or economically sterilized.It also provides obvious reduced risks of infection and complications, not to mention less stress on the animal.Although immunological castration agents are not yet ready for commercial use, such vaccines likely will be viable future alternatives to conventional castration methods.