No PERV transmission during a clinical trial of pig islet cell transplantation

Abstract

Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used. The animals were not genetically modified. The islet cells were transplanted in eight human recipients using a modified clinical protocol. Sera taken at different time points after transplantation (up to 55 weeks) were screened for the presence of antibodies against PERV proteins by Western blot analysis using viral antigens from highly purified virus particles. Positive sera obtained by immunization with recombinant PERV proteins were used as control sera. In none of the patients antibodies against PERV were detected, indicating the absence of infection. In parallel at different time points (up to 113 weeks) white blood cells (WBC) have been tested for PERV DNA, and WBC and plasma for PERV RNA by real-time RT-PCR. All tests were negative. In addition, using primers detecting pig mitochondrial cytochrome oxidase (COX) gene, patients were screened for microchimerism. In summary, the data are further evidence for the safety of pig islet cell transplantation.

Keywords: Clinical trial; Retroviruses; Virus safety; Xenotransplantation.