Managing potential zoonotic infections in swine-to-human islet xenotransplants

O. Garkavenko, D. Nathu, S. Wynyard, K. Durbin, R.B. Elliott
Living Cell Technologies, Auckland, New Zealand

Inxenotransplantation the area of concern is the diseases that may be transmittedto the recipient via the donor’s tissue.

Objective: The main objective of the study was to assessthe microbiological safety of swine-to-human islets xenotransplantation in donorpigs and 14 Type 1 diabetic patients in the New Zealand clinical trial.

Method: Directmethods for zoonotic pathogensidentifications such as PCR and High Resolution Melting Analysis (HRM) has beenused in the study. The pathogen screening list for donor pigs includes22 pathogens. Cellcultures susceptible for eco- and xenotropic pig endogenous retrovirus (PERV)such as HEK 293, MV1LU, ST. IOWA were used to assess infectious characteristicsof the virus. Fourteen diabetic patients were transplanted with alginate/polyornithinemicroencapsulated neonatal porcine islets with doses from 5000IEQ to 20000IEQ/kg.The patients were tested for the evidence of the xenotic infections at multipletime points by PCR using HRM and serology assays for swine infectious agentsincluding PERV.

Results: Large scale pre-clinical monitoring of the NewZealand pig population has been performed. A suitable source herd for islettransplantation has been identified and maintained. Donor pigs used in the study were free fromall tested potentially xenotic agents including infectious PERV. Assays for pig viruses have been developed andimplemented in long-term patient follow -up. Both qPCR and serology assays for PERV and all other pig viruses did notshow any evidence of infectious agents’ transmission in swine-to-humanxenotransplantation.

Conclusions: Extensive monitoring program for screening ofswine pathogens was developed and implemented for the New Zealand pigpopulation. The program is successful in identifying and maintaining the donorherd as suitable for islet transplantation. Assays for swine virusesidentification have been used to screen patients following isletxenotransplantation. There was no evidence of swine infection transmission.