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At least 433 records · Page 24Linked to original sources
PubMed1993

Immunocastration of colts and immunospeying of fillies.

A series of experiments using an ovalbumin conjugated gonadotrophin releasing hormone was used to stimulate antibody production, suppress testosterone secretion and depress testicular function in yearling and 2 year old colts and fillies. In the preliminary experiment, an injectable oil-based formulation was administered to yearling colts. Testicular development and testosterone secretion were retarded for a period of approximately 28-32 weeks while antibody titres were greater than 1:1000. An implant and water-soluble vaccine (200 and 400 mg) is presently being tested in 2 year old colts. Testicular dimensions and testosterone concentrations decreased following vaccination. Preliminary results indicate that the effects of the implant are reversible and last for approximately 30 weeks. The water-soluble vaccine produced effective antibodies for 10-19 weeks. Plasma testosterone of all colts was reduced to gelding levels (0.2 ng/mL) while antibody titres were greater than 1:1000. Semen evaluation, morphometric analysis and daily sperm production data indicate that the testes recovered normal function. These experiments are continuing and more definitive data on the vaccine and its reversibility will be available at their conclusion. Ovarian activity of the treated fillies (200 and 400 mg) ceased soon after vaccination. Their progesterone concentrations have remained below 1 ng/mL for 20 weeks. The untreated control fillies have continued to cycle normally as determined by ovarian ultrasonography and progesterone concentrations.

Animals↗
PubMed1997

Vaccines for control of fertility and hormone-dependent cancers.

This article traces and reviews the development of vaccines against two reproductive hormones, luteinizing hormone release hormone (LHRH) and human chorionic gonadotrophin (hCG). The heterospecies dimer (HSD)-dehydrogenase hCG vaccine is the first to have completed phase II clinical trials providing evidence for the prevention of pregnancy in humans by immunization with this vaccine. The vaccine acts without blocking ovulation or disturbance of menstrual bleeding. Its effect is fully reversible and fertility is regained with decline of the antibodies. The antibody response in humans is directed against immunodominant epitopes located in the core part of beta hCG, distinct from the C-terminal region. However, problems arising from carrier-conjugated vaccines against 'self' hormones such as carrier-induced immuno-suppression on repeated immunization are evoked and solutions discussed. The LHRH vaccine, a model semi-synthetic vaccine, can be used in both sexes and has applications in regulation of fertility of animals. It has therapeutic applications as a cost-effective approach in clinical conditions where LHRH agonists and antagonists have therapeutic action. The vaccine has undergone phase I and II clinical trials in advanced-stage carcinoma of prostate patients with encouraging results.

Cancer Vaccines↗
PubMed2003

Immunocontraception for population control: will resistance evolve?

The prospect for successful biocontrol using immunocontraception is threatened if there is adaptation to the vaccine through natural selection of individuals that are genetically resistant to the contraceptive agent. To assess this possibility we examined the literature and found that little relevant data are available for any species on the appropriate trait, fertility variation among immunized individuals, or about appropriate population and genetic parameters influencing the likelihood of a selection response. Some data are available on variation in antibody response to immunocontraceptives, but the relationship between antibody response and fertility levels is poorly documented. The antibody response data indicate low heritability for this trait suggesting that fertility levels of contraceptive-resistant individuals will also have a low heritability. Slow evolution of contraception resistance might therefore be anticipated. The absence of information about relevant parameters makes the construction of quantitative models premature. We discuss factors in particular need of investigation if predictions about resistance evolution are to be made. These include: 1. the genetic basis of fertility retention, 2. the proportion of the population resistant to the contraceptive agent and how this is affected by gene flow from refuge populations, 3. the genetically-based fitness tradeoffs of resistant individuals that often accompany selection, 4. cross-generation effects that can thwart the effects of selection, and 5. the efficiency of delivery of the contraceptive agent. An understanding of the above for particular species, and the development of appropriate divergently acting multiple vaccines that can be used in temporal rotation or in mixtures, should facilitate the development of management options to minimize resistance evolution.

Animals↗
PubMed2000

Molecular ecology and biological control: the mating system of a marsupial pest.

Many studies in molecular ecology have focused on the use of repeat DNA markers to determine the nature of mating systems in a wide variety of animal species. Whilst these studies typically have focused on important issues such as the evolutionary consequences of fitness variation among males, genetic studies of mating systems are potentially also important because they can generate information of significance to wider issues in wildlife management. For example, genetically modified, sexually transmitted viral diseases have been suggested as potential agents for the control of vertebrate pest species. An understanding of the epidemiology of such agents requires an intimate knowledge of the sexual contact rates between individuals of the target species. Here, we report the use of minisatellite DNA profiling to reveal the mating system in two New Zealand populations of the introduced Australian brushtail possum. The brushtail possum is New Zealand's most important mammalian pest and a species for which control by a sexually transmitted immunocontraceptive has been proposed. Encouragingly, we report considerable variation in the reproductive success of males at both study sites, with one male siring offspring from four females in one year (mean no. of offspring/reproductively successful male/year at the two sites is 1.95-2.15), while many sired none. This bias in the pattern of reproductive success among males will probably facilitate the spread of an immunocontraceptive agent and thereby increase the power of this approach to biological control.

Animals↗
PubMed1997

Plant-derived immunocontraceptive vaccines.

The use of transgenic or virus-infected plants to produce vitally needed vaccines for developing nations has been made possible by rapid advances in plant molecular biology and biotechnology during the last decade. Plant-based vaccines would be a welcome development for many impoverished countries that lack the capital-intensive infrastructure required to produce much-needed vaccines. The approach would also be ideally suited to the delivery of oral immunocontraceptive vaccines to a wide range of herbivore species. This review looks at the progress made to date in the use of plants for vaccine production, how this technology may be used in the future to deliver immunocontraceptive vaccines to free-ranging wildlife species, and the many problems that will have to be overcome if this promising approach is to ever 'bear fruit'.

Animals↗
PubMed1997

Case studies in wildlife immunocontraception: wild and feral equids and white-tailed deer.

Non-lethal management methods are required for wild equids that are protected by law and for deer inhabiting areas where lethal controls are not legal or safe. Single or multiple inoculations of porcine zona pellucida (PZP) vaccine have been delivered to wild horses and deer by means of darts. Contraceptive efficacy in horses after two inoculations ranged from 90% to 100%, and after a single inoculation ranged from 19% to 28%. Mares given a controlled-release form of the vaccine had foaling rates ranging from 7% to 20%. No detectable changes in social organization or behaviours among treated horses occurred. Contraceptive effects were reversible after 4 consecutive years of treatment but 5-7 years of treatment resulted in ovulation failure and decreased urinary oestrogen concentrations. Among deer, two inoculations were 70-100% effective in preventing fawns, but one inoculation yielded a contraceptive efficacy of < or = 20%, with pregnancies occurring late in the breeding season; a single annual booster inoculation reduced fertility to 20% in the second year. Energy costs of extended breeding seasons were less than those resulting from pregnancy. After two years of treatment, ovaries appeared normal. These studies suggest that PZP immunocontraception can be successfully applied to certain free-roaming populations of wild horses and deer.

Animals↗
PubMed1997

Immunocontraception in rodents: a review of the development of a sperm-based immunocontraceptive vaccine for the grey squirrel (Sciurus carolinensis).

The strategy for developing contraceptive vaccines for wild rodents will depend on the species. In rats and mice, high all-year birth rates, high levels of dispersal and promiscous mating systems suggest that, if immunocontraception was used alone, > 90% of the population would have to sterilized to achieve the desired control. In Britain, the grey squirrel (Sciurus carolinensis) may be a better candidate to investigate the feasibility of a contraceptive vaccine in rodents. This introduced species is a seasonal breeder with a much lower population turnover than rats or mice. As well as causing damage to woodland, it has ousted the native red squirrel (S. valgaris) from most of the UK. A human and selective method for the control of grey squirrels is therefore highly desirable. Numerous sperm-specific antigens have been identified on rodent spermatozoa. Monoclonal antibodies to particular components block sperm-egg interactions in laboratory animals and cross-react with grey squirrel spermatozoa. In vitro fertilization assays indicate that squirrel sperm-egg binding may be inhibited also. Currently, a cDNA library obtained from grey squirrel testis is being screened to identify genes encoding specific sperm antigens involved in fertilization. Methods of enhancing immunogenicity after oral immunization using microparticle carriers and immune-stimulating complexes are currently under investigation.

Administration, Oral↗
PubMed1997

Potential consequences and problems with wildlife contraceptives.

This presentation reviews multiple wildlife health considerations associated with contraception of wildlife, at the level of both the individual animal and wildlife population. Review of the literature demonstrates that many contraceptives studied in the past have had potential adverse effects characterized as follows: harmful effects on pregnant animals, inhibition of parturition or dystocia, changes in ovarian structure or function, changes in sex ratio, changes in lactation or mammary glands, impact on fertility of young, changes in testicular structure or function, changes in secondary sex characteristics, changes in bodyweight, changes in behaviour, changes in annual breeding season, other physiologic and pathologic changes, abscesses or inflammatory reactions, toxicity, interference with diagnostic tests and ecological alterations. Concern is expressed that the use of immunocontraception could create genetic changes in the target population that would influence disease resistance. The use of infectious agents as vectors to deliver immunocontraceptives was not considered wise animal health management because the product will be a new reproductive disease that could be difficult to contain within the target population. Criteria that need to be fulfilled for the safe use of contraceptives in wildlife are offered.

Animals↗
PubMed1997

Zoonoses and fertility control in wildlife--requirements for vaccines.

This paper reflects on public health considerations on the voluntary release of anti-fertility vaccines for wildlife in the environment. The World Health Organization (WHO) has established a variety of recommendations on safety and efficacy requirements for the voluntary release of rabies vaccines used for oral immunization of animals. These requirements cover aspects of control of rabies and possible biological consequences in the target population. They also deal with the protection of the health of humans and other non-target species that might come into contact with the different oral rabies vaccines used in various parts of the world. These recommendations are laid down in several WHO publications. They are specific to the disease concerned, the target animal reservoir, the relationship and types of contact between humans and target animals, the vaccines and baits used and the respective conditions of oral immunization of wildlife in densely-populated areas. Many of these recommendations also apply to the development and application of contraceptive vaccines for wildlife carnivores. Additional safety requirements concern the transmissibility of the antigen, the reversibility of the intervention within an individual animal and in animal populations, as well as the species specificity of the antigen used. The management of animal populations that are reservoirs for zoonotic diseases is a possible means by which diseases that are transmissible from animals to humans could be prevented. Oral contraception by means of vaccines is an appealing method, provided that requirements for protecting public and animal health, as well as ensuring environmental safety, are precisely defined and strictly adhered to.

Animals↗
PubMed1997

Can foxes be controlled by reducing their fertility?

A model based on data from research in New South Wales conducted by the Cooperative Research Centre for the Biological Control of Vertebrate Pest Populations suggests that the effectiveness of fertility control in reducing the abundance of foxes (Vulpes vulpes) can be strongly influenced by environmental variability. The model includes age-specific recruitment and survival as functions of resources indexed by rainfall. It is assumed that fertility control will affect only female foxes and that the use of a baiting regime to deliver a contraceptive agent will result in fixed proportional changes in pregnancy rates. By comparing the variability in the rate of increase of treated and untreated fox populations, the model predicts that: (i) frequent baiting, every one or two years, will be more effective than applications of baits at longer time intervals; (ii) the abundance of foxes will decline more rapidly, with higher levels of fertility control; (iii) infertility which lasts for only one breeding season is less effective than permanent sterility which allows for accumulation of sterile animals in the population; and (iv) highly variable results are likely to be the outcome of low-frequency baiting with an agent that produces only temporary infertility.

Animals↗
PubMed1997

Cytokine enhancement of immune responses important for immunocontraception.

To be effective, an immunocontraceptive vaccine should elicit strong, sustained antibody responses. Circulating antibodies may block the function of hormones and target some gamete antigens, but the most effective inhibition of fertilization will probably be achieved by antibodies in the reproductive tract. It may also be beneficial to administer vaccine antigens with strong adjuvants, such as cytokines, in order to achieve high specific antibody titres. In this review recent findings concerning the role of cytokines in the regulation of antibody responses, particularly at mucosae, are described and prospects for immunization for immune responses which may be important for fertility control are discussed. On the basis of these findings, a model system for the delivery of vaccine antigens to the immune system in vaccinia, fowlpox or DNA plasmid vectors along with type-2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-6, as B cell adjuvants is presented. Studies such as these in the areas of antigen delivery and enhancement of immune responses are aimed at providing new options for fertility control, particularly via oral vaccination.

Animals↗
PubMed1997

Development and use of virus-vectored immunocontraception.

Virus-vectored immunocontraception (VVIC) is perceived to present biological risks, real or baseless, which create social and political constraints to deploying VVIC for managing vertebrate pests. Developing and deploying VVIC must be justified and address biological, social and political risks. Future needs for pest management will influence deployment of VVIC. Projections of human society and pest impact on agriculture and conservation suggest increasing need for cost-beneficial strategies. Best strategies are likely to integrate various methods, possibly including forms of VVIC. Processes identifying future pest impacts and roles for VVIC are shown using the rabbit in Australia. Present research developing VVIC aims to test physiological feasibility, to develop it for specific pests, and address aspects of ecological feasibility. Minimizing biological risks through choosing species-specific antigens and, if possible, viral vectors, is central and overseen by regulatory authorities. International collaborators study related valued species to develop protective strategies. Excellent science can withstand legal or public challenge to safe and cost-beneficial VVIC if aided by information needed by the public exposed to media distortion of scientific debate, complex argument and concepts of probability and risk. Sound science needs support from strategies for public processes to enable cost-beneficial management of vertebrate pests.

Animals↗
PubMed1997

Progress towards using recombinant myxoma virus as a vector for fertility control in rabbits.

The history of myxoma virus, its use in Australia as a mortality agent and the development of the virus as a vector for controlling fertility in wild rabbit populations in Australia is reviewed. Myxoma virus recombinants have been constructed to express model antigens. Four potential insertion sites in the genome have been identified and two have been used to construct single and double recombinant viruses expressing Escherichia coli enzymes beta-galactosidase and beta-glucuronidase. Another recombinant expressing an influenza virus haemagglutinin gene (A/PR8/34) induced high and sustained antibody responses following intradermal inoculation in rabbits. To demonstrate the potential of introducing a recombinant virus into wild rabbit populations, a virus containing a natural deletion was released at four field locations. Preliminary analysis of the data has shown that the introduced virus spread well on 3 of the 4 locations. The steps being taken to address the ethical and safety implications of the introduction of a recombinant virus into the field are discussed.

Animals↗
PubMed1997

Modelling immunocontraception in disseminating systems.

Vectored immunocontraception is a novel technology and simple models are described to help predict whether, and how, it might work. That is, given that an effective immunocontraceptive agent can be produced, and given that it can be inserted into a microparasitic or macroparasitic infective vector, would the vector persist and reach a high prevalence in the host and, if so, would it sterilize a sufficient proportion of the host breeding population to significantly reduce its density? Both conditions are necessary for success. The first question is an epidemiological one, relating solely to disseminating systems and differing according to whether the vector itself is newly introduced or pre-existing. If it is newly introduced, the assumption is that it is present in some other geographical areas occupied by the same target species, or is found in closely-related species. If the vector already exists in the population, the issue is one of competition between the engineered and wild-type vectors. The second question is an ecological one, common to both non-disseminating and disseminating systems. Whatever level of sterilization the immunocontraception provides must translate into a significant reduction in population density, having regard to the nature and extent of compensatory, density-dependence mechanisms in the population. These two questions, together with other more minor issues, are addressed in turn with particular reference to models for immunocontraception of brushtail possums (Trichosurus vulpecula) in New Zealand.

Animals↗
PubMed1997

Likely targets for immunocontraception in marsupials.

There is a growing need to manage marsupial populations as a means to mitigate economic and environmental damage and resolve animal welfare problems. In Australia, the problems of population management are highly specific and localized. In contrast, in New Zealand the problem is the control of the many millions of widely-distributed brushtail possums which are the country's major vertebrate pest. The needs of the two countries are thus very different but immunocontraception may provide an effective and humane alternative to current lethal control strategies. This paper discusses the features of marsupial reproduction and development that offer potential as targets for immunocontraceptive interference, including: (1) sperm production and maturation in the male; (2) sperm transport and maturation in the female; and (3) sperm and egg antigens and the early embryo. Some of these antigen targets are shared with eutherian mammals but others are likely to be unique to marsupials.

Animals↗
PubMed1997

Selection of antigens for use in a virus-vectored immunocontraceptive vaccine: PH-20 as a case study.

The European wild rabbit (Oryctolagus cuniculus) has become the major agricultural and environmental pest species in Australia. Current methods of rabbit control are lethal procedures which are increasingly questioned for their overall efficiency, applicability, specificity, cost and humaneness. New initiatives are required. One such initiative is virus-vectored immunocontraception. In this approach, the lagomorph-specific myxoma virus will be genetically engineered to include genes encoding components of rabbit gametes which can induce an immune response that causes infertility. Central to such a strategy is the ability to identify antigens capable of inducing an immunocontraceptive response. A strategy for identifying such antigens has been described previously. A case study of one sperm antigen, PH-20, is reported here. The issues involved in developing this antigen to the stage where it could be considered as a candidate for insertion into a recombinant myxoma virus with the ultimate goal of testing for immunocontraceptive efficacy are discussed. Techniques for inserting genes into myxoma virus have been described previously. The knowledge gained from research with this particular antigen are broadly applicable to other antigens used for both immunocontraceptive vaccines in general and, specifically, for virus-vectored immunocontraception.

Animals↗
PubMed1998

Cloning and characterization of the cDNA encoding the PH20 protein in the European red fox Vulpes vulpes.

The PH20 protein is thought to play a crucial role in mammalian fertilization. The fox PH20 homologue has been cloned from a testis cDNA library and the deduced protein sequence shows high levels of homology to PH20 proteins isolated from other species. Unlike other PH20 proteins the fox protein does not appear to be membrane associated through a GPI-linkage nor does it show the presence of a transmembrane domain at the C-terminus of the protein. It is in this region that the proteins appear to be least conserved. Immunolocalization studies on fox sperm show that the PH20 protein is located on the inner acrosomal membrane. Transcription of PH20 in the fox is seasonally regulated, with the mRNA expressed during those months when spermatogenesis is at its peak. The PH20 sequence described in this paper has been submitted to the Genbank database and has the accession number U41412.

Amino Acid Sequence↗