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At least 451 records · Page 25Linked to original sources
PubMed2001

Biotech prospects for the control of introduced mammals in Australia.

More than twenty exotic vertebrate species are now listed as pests in Australia. Collectively, these pests have a huge economic and environmental impact and pose a major threat to Australia's ecosystems and unique biodiversity. Management of such pests on a continental scale is a major challenge. Recent advances in biotechnology suggest alternatives to the lethal diseases normally sought for use as biological control agents. One proposal, being investigated in the Pest Animal Control Cooperative Research Centre, Canberra, is the use of biotechnology to develop a new generation of agents that act through controlling reproduction to prevent the build up of pest populations. The core concept is fertility control through immunocontraceptive vaccines delivered by viruses that specifically infect the target pest population. Proof of this exciting concept has been obtained for the mouse and, very recently, the rabbit, and a candidate vaccine vector identified for the fox, portending better control of a trio of Australia's most pervasive pests. Other advances in biotechnology suggest ways to negate the build up of both innate and acquired immune resistance in target pest populations that normally act to limit the efficacy and effective life of biocontrol agents in the field. Prospects for extending the use of virally vectored vaccines to the field management of wildlife diseases are also identified. Targets for such vaccines include a growing suite of emerging diseases, hosted by Australia's wildlife, which pose a threat to human and livestock health. Numerous technical challenges remain to be addressed before any of these new agents are ready for use in the field. However, the major risk to their development is now no longer viewed as being technical, but the failure to gain public acceptance for their use in the field. This already significant risk is exasperated by the present heightened level of public concern about all introductions of genetically modified organisms.

Animals↗
PubMed2002

Assessment of the immunocontraceptive effect of a zona pellucida 3 peptide antigen in wild mice.

Immunizing laboratory mice against a short peptide to mouse zona pellucida protein 3 (mZP3; amino acids 328-342) reduces fertility in some strains. This antigen was therefore tested to see if it is suitable for use in an immunocontraceptive vaccine to control wild mice. Mouse zona pellucida protein 3 peptide conjugated to a carrier protein (keyhole limpet hemocyanin) was considerably more immunogenic and effective in reducing fertility in wild mice when compared with inbred BALB/c mice. Fertility of the immunized wild mice was reduced by over 50% compared with controls, whereas BALB/c mice showed no reduction. Variation in the responses between individual animals to mZP3 peptide was observed and infertility correlated to the presence of cross-reacting antibodies to native zona pellucida in wild, but not BALB/c, mice.

Animals↗
PubMed2002

Porcine zonae pellucidae immunization of tammar wallabies (Macropus eugenii): fertility and immune responses.

This study looked at the feasibility of targeting the zona pellucida for a contraceptive vaccine as a possible alternative method of control for overabundant macropods. Tammar wallabies, as a model for other macropods, were immunized with porcine zonae pellucidae (PZP) and were found to achieve significant concentrations of antibody to PZP in sera and reproductive tract fluids. Wallabies immunized with PZP exhibited lower ovarian weight with reduced numbers of antral follicles when compared with control animals. Wallabies were placed in a natural mating trial followed by an artificial insemination trial. None of the PZP-immunized wallabies produced offspring in the natural mating trial compared with 67% of control animals. To further assess fertility, a sub-sample of the wallabies were superovulated and artificially inseminated. This resulted in all control wallabies producing fertilized ova and all PZP-immunized wallabies failing to ovulate. These results suggest that immunocontraception based on targeting antigens of the zona pellucida may be an effective strategy for fertility reduction in macropods.

Animals↗
PubMed1999

Antigen-specific systemic and reproductive tract antibodies in foxes immunized with Salmonella typhimurium expressing bacterial and sperm proteins.

Attenuated Salmonella typhimurium strains are potential 'safe' delivery vectors of an oral immunocontraceptive vaccine for the European red fox (Vulpes vulpes). In the present study, model bacterial (Escherichia coli heat-labile enterotoxin B subunit, LTB) and fox sperm (fSP10) antigens were expressed in S. typhimurium SL3261 (delta aroA) under the control of the trc promoter. Adult female foxes were given three oral immunizations with SL3261 containing either LTB (SL3261/pLTB), fSP10 (SL3261/pFSP10) or a control plasmid (pKK233-2 or pTrc99A). All foxes raised serum (IgG) and vaginal (IgG and IgA) antibodies against S. typhimurium lipopolysaccharide (LPS). Each fox that received SL3261/pLTB raised high titre LTB-specific serum and vaginal IgG antibodies. However, only one of four foxes immunized with SL3261/pFSP10 raised an anti-fSP10 immune response, in the form of low titre serum and vaginal IgG antibodies. No vaginal IgA antibodies were raised against either LTB or fSP10 in these experiments. The immune responses against recombinant LTB and fSP10 resulted chiefly from the initial dose of antigen in the inocula and were minimally influenced by continued in vivo antigen expression. This study demonstrates for the first time in the female red fox that oral Salmonella can elicit specific systemic and reproductive tract antibodies against heterologous, recombinant proteins.

Acrosome↗
PubMed1994

Virus-vectored immunocontraception of feral mammals.

The potential value of immunosterilization as a means to control species of wildlife that are widespread, numerous and undesirable is assessed. Key questions about the efficacy of fertility control and the means for delivering antigens expressed in recombinant viral vectors are discussed and the legal and social concerns that relate to its possible future use are raised.

Animals↗
PubMed1994

Experimental strategies for the development of an immunocontraceptive vaccine for the European red fox, Vulpes vulpes.

The development of an immunocontraceptive vaccine to control fox populations in Australia would confer considerable advantages in controlling the long-term impact of this predator on native and endangered species. Studies are currently under way to identify sperm antigens that might be used in such a vaccine, and some of these studies are described. It is proposed that such a vaccine would be delivered orally in a bait, thereby stimulating a mucosal immune response to the foreign antigen(s). Such a vaccine requires a detailed understanding of reproductive-tract mucosal immunity in foxes, and selection of the most effective form of antigen delivery. Those under consideration include viral or bacterial vectors and microencapsulated antigens.

Animals↗
PubMed1994

Disease and fertility control in wildlife and feral animal populations: options for vaccine delivery using vectors.

A wide variety of vertebrates have been introduced into Australia during the 200 years of European settlement. Many have become pests causing significant environmental damage and having the potential to act as reservoirs of infectious diseases. Control of vertebrate pest species by fertility control is attractive on animal welfare grounds. Should exotic animal diseases become established in any of these feral animal populations vaccination would be an essential element in the control or eradication of disease. The only experience to date with vaccination of wildlife or feral animals has been the successful control of rabies in foxes in Europe by means of a live, attenuated rabies vaccine and a vaccinia-rabies recombinant vaccine. The feasibility of vaccination for disease control or fertility control in other vertebrate pests will depend on the development and evaluation of several vaccine vector strategies. The choice of vector, based on live viruses or bacteria, naked DNA coding for vaccine antigen or virus-like particles encapsidating genetic material coding for vaccine antigen, will depend on optimization of vector delivery strategies and immunogenicity of the vaccine antigen. Past experience from the vaccination of foxes against rabies suggests that rates of uptake of the vaccine bait and immunogenicity of the vaccine will be crucial factors in determining the success of other vaccines controlling disease or fertility.

Animals↗
PubMed1994

The potential of murine cytomegalovirus as a viral vector for immunocontraception.

Wild populations of house mice (Mus domesticus) regularly undergo population eruptions in the cereal growing regions of S.E. Australia, causing significant damage to crops. Rodenticides are costly and are of limited usefulness, and the need for a biological control agent is widely recognized. The options for the use of an infectious agent to control mouse populations are considered. The three main types are: infectious agents which establish lethal infection; those which directly interfere with fertility; and recombinant virus vectors encoding fertility-associated proteins such as zona pellucida or sperm antigens in order to induce immunocontraceptive responses in infected mice. Ectromelia, a murine pox virus, has the potential for reducing mouse populations by lethal infection but it is not present in wild mice in Australia. The disadvantages of using ectromelia are that it would pose a significant threat to colonies of laboratory mice, there appears to be substantial innate resistance in Australian wild mice and it may not be entirely mouse-specific, thus placing native rodents at risk. A number of factors influencing the selection of a virus as a vector for immunocontraception are discussed. The mouse-specific murine cytomegalovirus (MCMV) fits most of these criteria. Infection with MCMV is already widespread in Australia with 80-90% of Mus domesticus tested being seropositive. It is a large DNA virus which establishes persistent, non-lethal infection, it is a suitable vector for the insertion of foreign genes and has a number of properties, including the capacity for superinfection, that should assist the recombinant virus to persist in wild mouse populations and induce an immunocontraceptive effect.

Animals↗
PubMed1994

Virus-vectored immunocontraception for control of wild rabbits: identification of target antigens and construction of recombinant viruses.

The need to control animal populations arises in many situations in the world from a variety of motives. Present control strategies are almost universally based on lethal procedures. Increasingly, there is dissatisfaction with such approaches from many different perspectives. In response to these concerns, the concept of controlling populations of pest species through control of their fertility has been mooted. Successful examples of this approach exist in cases of small, discrete pest populations but application of this to a widely distributed species over a broad geographical area has not yet been achieved. In this article, we report on a new approach to fertility control, virus-vectored immunocontraception, and discuss its applicability to control of wild rabbit populations. Particular emphasis is placed on the strategy for selection of a target molecule capable of inducing an immunocontraceptive response and on how the gene encoding such a molecule might be engineered into the myxoma virus for distribution into the population. The fact that the procedures for antigen identification and the viral engineering methods used are, to varying extents, generic means that the broad principles of this approach are applicable in other species.

Animals↗
PubMed1995

Sperm antigens and immunocontraception.

The development of novel forms of contraception is one way in which the world population crisis is being tackled. The concept of a contraceptive vaccine based on gamete-specific antigens is a particularly attractive approach. Much research has been carried out to identify sperm antigens which could be used as the immunogen. The most encouraging leads have come from groups using monoclonal antibodies to identify and characterize sperm antigens important for fertility (e.g. SP-10, PH-20 and PH-30). Identification of these molecules will also enable the development of specific tests for the diagnosis of immune infertility.

Antibodies, Monoclonal↗
PubMed1997

Fertilization antigen-1: cDNA cloning, testis-specific expression, and immunocontraceptive effects.

cDNA encoding for a sperm antigen, designated fertilization antigen (FA-1), was cloned and sequenced from murine testis cDNA-lambdagt11 expression library using FA-1 mAb. Computer-generated translation analysis of 649-bp cDNA yielded an ORF of 164 amino acids with the first ATG Met start codon at nucleotide 81 and the stop codon TAA at nucleotide 577 and a polyadenylylation tail following the stop codon. The translated protein has a calculated molecular mass of 18.2 kDa and a potential N-linked glycosylation site at amino acids 158-160, besides at least two O-linked glycosylation sites. The hydropathy plot generated from the deduced amino acid sequence indicated it to be a membrane-anchored peptide. Extensive computer search in the GenBank, National Biomedical Research Foundation, and Swiss sequence banks did not identify any known nucleotide/amino acid sequence having homology with FA-1 cDNA or deduced amino acids, indicating it to be a novel protein. Northern blot analysis and reverse transcription-PCR indicated testis-specific expression of FA-1 antigen. The FA-1 cDNA was subcloned into pGEX-2T vector and expressed in glutathione S-transferase gene fusion system to obtain the recombinant protein. The recombinant protein specifically reacted with ZP3 of oocyte zona pellucida and its affinity-purified antibodies completely blocked sperm-zona pellucida interaction in mice. These findings suggest that the sperm-specific recombinant FA-1 antigen is an attractive candidate for the development of a contraceptive vaccine.

Amino Acid Sequence↗
PubMedDate not supplied

Effect of immunization with synthetic peptide corresponding to region 1-17 of human seminal plasma inhibin on fertility of male rats.

Immunization of adult male rats with a synthetic peptide corresponding to the region 1-17 of human seminal plasma inhibin (hSPI) resulted in agglutination of epididymal sperm, severely affecting the fertility of the animals (75% reduction in fertility as compared to control). This effect was found to be dependent on the antibody titer to hSPI. There was a significant rise in circulating follicle-stimulating hormone levels, with luteinizing hormone and testosterone levels remaining unaffected. The histology of the testes and other reproductive organs revealed that these organs remained unaltered. The N-terminal 1-17 amino acid peptide of hSPI may hold promise as an immunogen for male immunocontraception.

Animals↗
PubMed2004

Application of a gene vaccine targeting HER-2/neu in immunocontraception.

HER-2/neu was widely used as a target for tumor prevention and therapy because of its overexpression in many tumors. However, it also plays an important role in proliferation of endometrium, embryo implantation, and development. Here, HER-2/neu was used in immunocontraception. A gene vaccine encoding the extracellular domain of human HER-2/neu was constructed. After immunization, it especially elicited both humoral and cellular responses in mice. Embryo implantation was interfered by intravenous and intraluminal injection of anti-HER-2/neu serum or lymphocytes. Lower fertility was induced after vaccination when compared with the control groups, while injuries to the uterus and ovary were not observed. Our results suggested a new and impactful target for contraceptive vaccines development.

Animals↗
PubMed1995

Targeting the zona pellucida for immunocontraception: a minireview.

This minireview summarizes the main data relevant to the development of contraceptive vaccines based on zona pellucida (ZP) antigens, as well as the pros and the cons of this immunocontraceptive strategy. Even though the antifertility efficacy of anti-ZP antibodies in humans is not corroborated by a clear relationship between spontaneous autoimmunization against the ZP and infertility, passive and active immunization studies in laboratory animals have provided convincing results. The contraceptive action of anti-ZP antibodies, targeting events situated upstream of gamete fusion, is devoid of potential ethical concerns related to the destruction of early embryos. The high protein content of the mammalian ZP, knowledge of the complete amino acid sequence of the major ZP proteins, and the high degree of sequence homology between individual species all favour the rapid advancement of anti-ZP vaccine projects. However, certain sequences of ZP proteins, when incorporated into the vaccine construct, activate CD4+ T cells of the recipient organism to direct a cellular immune attack (autoimmune oophoritis) to other functionally relevant ovarian components (primordial follicles, steroidogenic cells). The search for the optimal combination of B cell and T cell epitopes in the vaccine construct will hopefully overcome this problem.

Antigen-Antibody Reactions↗
PubMed1997

Immunoreactivity and in-vitro effect on human sperm-egg binding of antibodies against peptides corresponding to bonnet monkey zona pellucida-3 glycoprotein.

The following synthetic peptides were made as immunogens for development of a zona-based contraceptive vaccine: P1, KQPFWLLQGGASRAETSVQPVLVE [amino acids (aa) 23-45 with an additional K at the N-terminus]; P2, FSEEKLVFSLRLMEENC (aa 164-179 with an additional C at the C-terminus and T170 replaced by V); and P3, CSFSKSSNSWFPVEGPADICQCC (aa 300-322). The aa are numbered on the basis of bonnet monkey ZP3 precursor protein. Antibodies against an additional peptide P4, KGDCGTPSHSRRQPHVVSQWSRSA (aa 324-347), significantly inhibits human sperm-oocyte binding. In addition, antibodies against cocktail of peptide-diphtheria toxoid conjugates also significantly inhibit the binding of spermatozoa to zona pellucida in a hemizona assay. These results will further help in the design of an immunocontraceptive vaccine based upon synthetic peptides corresponding to ZP3.

Amino Acid Sequence↗
PubMed1997

Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: results of a pilot study.

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non-specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

Adult↗