Speaker
Description
Introduction:
Most current animal vaccine regimes involve a primary vaccination followed sometime later by a booster vaccination. This presents challenges when vaccinating difficult to access animals such as livestock. Mustering livestock to deliver a vaccine boost is costly and stressful for animals. Thus, we have produced a platform system that can be administered at the same time as the priming immunisation and delivers payload after an appropriate delay time to boost the immune response, without need for further handling of animals.
Methodology:
Sixteen, female Merino crossbred sheep were split into two groups of 8. Group 1, (n=8) was immunised by subcutaneous injection with 2.5 Lf clostridial toxoid (VirBac Australia) combined with 20% Alhydragel® adjuvant, at days 0 and 30. Group 2, (n=8) was immunised by subcutaneous injection with clostridial toxoid (VirBac Australia) combined with Alhydragel® adjuvant on day 0 as well as a subcutaneous vaccine implant containing the 2.5 Lf units of toxoid, Rehydragel adjuvant and glucose combination. The implant had been designed to release the payload at day 30 post-insertion via burst release due to osmotic pressure.
The vaccine implants were made from medical grade poly(ε-caprolactone) (mPCL). The implants were prepared by dip-coating onto 2 mm outer diameter brass rods (Precision Metals, USA). A stock solution was prepared by dissolving 15.0 g of mPCL in 100 mL of chloroform overnight.
Blood samples were collected over 12 weeks along with weight and temperature data. This was used to assess humoral and cell-mediated immune responses through ELISA and T cell proliferation. After 12 weeks the sheep that received the vaccine implant were euthanised and the implant plus surrounding tissue was excised to assess histologically and immunohistochemically.
Results:
The two groups showed identical weight gain curves over 12 weeks. T cell proliferation following in vitro stimulation with antigen was identical between the two groups at all time points. However, serum IgG antibody responses to the tetanus toxoid antigen were significantly higher in the control group at weeks 8 and 12. The implant capsules stayed at the site of implantation and at week 12 macrophages and lymphocytes were the predominant inflammatory cells surrounding the implant admixed with mild to moderate amounts of collagen deposistion. Through the use of collagen, blood vessel and macrophage staining, good tissue integration and regeneration was shown. No local reactions at the implant site were observed, other than mild thickening of the skin in half of the implant group animals and no other adverse health events were recorded in either group over the 12 weeks.
Conclusions:
We have used a sheep model to compare the potential of a controlled-release polymeric vaccine implant, delivered at the same time as the primary vaccination to elicit cell-mediated and antibody immunity against tetanus toxoid. While the implants did stimulate equivalent T cell responses, there were significant differences between the group’s antibody responses, possibly due to antigen degradation or incomplete rupturing of the capsule, this study still serves as a good starting point for optimising the capsule in in vivo studies.
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