Reproduction in Domestic Animals

182 R Fayrer-Hoskenvaccine duration and efficacy is the magnitude andduration of serum antibody levels. For the nativeantigen, to all intents and purposes, its antigenicstructure is similar for preparations from the samelaboratory. This is not the case in synthetic preparationswhere the selected DNA sequence and expressionsystem affect the product.Duration of immunocontraceptionMost of the above-mentioned adjuvants provide at least12 months of immunocontraception with one or twoboosters. Some reports indicate longer effects with otherpreparations (Liu et al. 2005) with no boostering or onebooster. The 1-year duration vaccines can be administeredfor several years without any side-effect. However,after multiple seasons of administration, there areovarian effects as seen with the horses on AssateagueIslands. These cases that have an oestrogen phase ofoestrus, but did not appear to initiate a luteal orprogesterone phase. The initial (>5 years) effect oncyclicity of mares is reversed after several years when novaccines have been re-administered. Pregnant animals(Fayrer-Hosken et al. 2000b; Kirkpatrick and Turner2002) can be vaccinated with no deleterious effects onthe foetus and growth of the offspring. These offspringhave been shown to grow normally and are fertile asadults.Current vaccinesCurrent vaccines use synthetic or recombinant ZPfragments with or without glycosylation, DNA vaccinesor virally vectored vaccines. How does the structure ofthese antigens affect fertility and by what mechanism dothey function? The selection of the specific portions ofthe DNA for the production of ZP glycoproteins is thecurrent optimal technology. The selection of the ZPsequence is very important when an expression systemis selected. Immunocontraceptive antigens can beexpressed in bacterial systems (Hardy et al. 2008), yeastsystems (Tang et al. 2003), Chinese hamster ovary(CHO) systems (Zhao et al. 2004), plant systems (Tacket2005), viral systems (Hardy et al. 2003), insect systems(Hardy et al. 2003; Choudhury et al. 2007) and mammaliancell lines. The recombinant products of thesesystems have several exciting properties. The antigenpurity and structure are optimized. The purity (Tanget al. 2003) of purified native proteins has been aconcern and the effect of contaminating antigens has notbeen clearly documented. Once the appropriate antigenand expression system has been discovered for a specificspecies, abundant amounts of the antigen could beproduced in a cost-effective and repeatable process.These antigens and their production systems will be thefuture zenith of fertility control vaccines. Anotherstrategy is to use a species-specific antigen with aspecies-specific virus to produce a virally vectoredimmunocontraceptive (Redwood et al. 2007). Thevirally vectored immunocontraceptive would solvemany of the practical problems of fertility control ofpopulations. Nevertheless, there is a concern that viralor antigen mutation could lead to the doomsday virus.SummaryThe ZP vaccine is the most tested antigen fromlaboratory to field application. The vaccine appearssafe and effective. The fertility control vaccine does notappear to adversely affect the sociobiology of the targetspecies.Role of hormonal targets for vaccines to control fertilityFertility control can also be achieved by the vaccinationof male or female animals with antigens that arehormones. Several successful studies have been reportedusing gonadotropin-releasing hormone (GnRH) orluteinizing hormone releasing hormone (LHRH),human chorionic gonadotropin (hCG) and folliclestimulatinghormone (FSH).GnRH ⁄ LHRHThe hormonal vaccines can be used as fertility controls,and also as therapeutic agents. Treatment of endocrinedisorders and neoplasms is an important facet ofhormonal vaccines. A GnRH vaccine in humans as atherapeutic agent is increasingly important. The classicalGnRH or GnRH-I is the main hormone and alterationsto its secretions will affect ovaries, testis, prostate andplacenta. The GnRH vaccine has been used successfullyin multiple species. The GnRH vaccine must be conjugatedto a hapten or produced as a recombinant vaccinecontaining an immunogenic moiety in order to amplifythe antigenicity of the decapeptide. Conjugation toKLH, ovalbumin, more potent adjuvants or otheramplifying agents is the essential for efficacy. It hasworked for variable periods of time in both sexes in pigs(Killian et al. 2006), sheep (Earl et al. 2006), horses(Turkstra et al. 2005; Imboden et al. 2006; Elhay et al.2007), deer (Curtis et al. 2002) and bison (Miller et al.2004). The primary problem associated with GnRHvaccines is to produce durable titres.Over the years, several commercial preparations havebeen developed and marketed with greater or lesserfunctional product. Current preparations include GonaConÔ,ImprovacÔ (Dunshea et al. 2001), Equity andRepro-BlocÔ. The GnRH-analogue, GnRH-d6-Lys,was conjugated to recombinant Mycobacterium tuberculosishsp70 and adjuvanted with RIBI (STDCM) orIncomplete Freund’s was used in pre-pubertal mice.There was a statistically significant effect on the size ofthe urogenital complex and testosterone levels (RIBI).One of the most important animal uses of the GnRH-D6-Lys vaccine is in beef production. This product is animportant alternative to hormonal growth promotersand their side-effects. The vaccines have the desiredeffects through multiple treatments on both sexes withminimal side-effects. This is a quality product for thecaptive environment, but for wild populations, themultiple administrations pose the same problems aspZP vaccines. Depending on the presentation andadjuvantation, GnRH vaccines last from 1 to 2 years(Miller et al. 2000). The return to fertility with GnRHvaccines is more rapid than pZP vaccines. In the shortterm with GnRH vaccines, there is a cessation ofÓ 2008 The Author. Journal compilation Ó 2008 Blackwell Verlag