B.AWW.0260 - Development of a single shot immune-contraceptive vaccine for cattle
A practical alternative to spaying cattle is being sought by industry to improve beef cattle wellbeing.
| Project start date: | 31 October 2017 |
| Project end date: | 29 May 2024 |
| Publication date: | 01 August 2024 |
| Project status: | Completed |
| Livestock species: | Grass-fed Cattle |
| Relevant regions: | National |
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Summary
Spaying of cows has been shown to significantly improve productivity in extensively managed beef herds where continuous mating is common practice and reduce farm deaths in cull cows. Spaying is commonly done without the use of pain relief, which causes significant pain, stress and typically 1 to 4% of treated cattle die of surgical complications. Vaccination against the zona pellucida (ZP), the outermost layer of the egg, would provoke an immune response with antibodies binding to the ZP preventing fertilisation for 12 months.
Objectives
The primary aim was to develop an immunocontraceptive vaccine capable of preventing cattle from becoming pregnant for a period of approximately 12 months following a single vaccination. The objectives were to identify:
1) Which porcine (p) ZP proteins should be incorporated in a vaccine
2) How the vaccine should be formulated to enable infertility to be induced following a single vaccination
3) Which synthetic (recombinant) ZP protein construct/production system should be used to produce selected ZP protein(s) able to be incorporated in a commercial vaccine.
Key findings
- A practical method of producing large amounts of pZP suitable for cattle vaccination studies was developed.
- pZP3 and pZP4 are apparently tightly bound and were purified as a complex rather than individual proteins.
- Administration of vaccines to cycling heifers containing either purified pZP2 or pZP3&4 suspended in Freund’s adjuvant (Exp.1) induced prolonged infertility in a high proportion of heifers (71% and 100% first mating, 71% and 78% second mating, respectively).
- Single administration of a vaccine containing a recombinant heterocomplex of bZP3&4 suspended in an emulsion of MontanideTM ISA VG 61 to cycling heifers induced infertility in some heifers initially. The outcome of two further mating periods is required to confirm and better understand this finding.
- As with all vaccines, there was some evidence that even where an effective response was obtained there were a few animals which failed to respond.
- There was some evidence that pZP vaccination may be reversible.
Benefits to industry
This project has demonstrated that an immunocontraceptive vaccine targeting the zona pellucida could be developed for use in cattle, but more work needs to be done to create better quality recombinant ZP proteins. Vaccination of cattle with either pig derived or recombinant ZP/ZP proteins was shown to have little or no impact on their health, well-being, growth and carcase quality, however the latter failed to induce infertility in most vaccinated cattle. There was evidence that some vaccinated cattle could recover fertility after approximately 12 months, but this was not examined in detail. An outline for implementation of a single shot immunocontraceptive vaccine was developed in consultation with a senior cattle veterinarian servicing beef cattle businesses in northern Australia.
MLA action
Further research into this area has been incorporated into MLA's FY25 business plan.
Future research
The failure of the administered recombinant pZP protein vaccines to induce infertility in a high proportion of heifers represents the major challenge for future research. It seems likely that the failure of the recombinant ZP protein vaccine to induce infertility was due to significant differences in glycosylation and conformation between the native pZP and the recombinant ZP. Glycosylation is a complex and critical process playing an important role in the biological activity, folding, stability and solubility of proteins. Failure of a recombinant protein to fold into the correct three-dimensional structure typically results in the production of inactive proteins. These are some of the well-recognised challenges in producing recombinant protein vaccines. In addition, as there was evidence that vaccination against purified pZP2 protein induced infertility in a significant proportion of heifers development of a method of producing recombinant ZP2 should be investigated.
More information
| Project manager: | Michael Laurence |
| Contact email: | reports@mla.com.au |
| Primary researcher: | University of Queensland |
