Absence of PERV specific humoral immune response in baboons after transplantation of porcine cells or organs

Abstract

Xenotransplantation of pig organs seems a promising way of overcoming the prevailing limitation on allotransplantation due to donor numbers. However, as porcine endogenous retroviruses (PERVs) can infect human cells in vitro, there is substantial concern regarding the risk of a PERV infection in xenogeneic transplant recipients. Cultured porcine endothelial cells, stimulated peripheral blood mononuclear cells, and pancreatic islet cells can release PERV infectious for human cells in vitro, but it is currently unknown whether PERV is released in vivo, whether these viral particles can infect the transplant recipient, and whether they are pathogenic. In a retrospective study 15 immunosuppressed baboons were tested for a specific immune response against PERV after transplantation of porcine endothelial cells, mononuclear blood cells, and lungs. Anti‐PERV antibody expression was analyzed with peptide‐based, enzyme‐linked immunosorbent assays and highly sensitive Western Blot assays. This xenotransplantation study using nonhuman primates found no evidence of PERV specific humoral immune response. Our data suggest that no productive PERV infection and no continuous PERV release takes place in the nonhuman primates analyzed in this study.

Porcine Endogenous Retroviruses PERV-A and PERV-B Infect neither Mouse Cells in vitro nor SCID Mice in vivo

“…The establishment of a suitable animal model would, therefore, be invaluable for evaluating the potential risks posed by PERVs during xenotransplantation. However, all attempts to infect small animals and nonhuman primates have so far failed, although cells from some of the species tested, including mink, baboon and rhesus monkey, could easily be infected in vitro [25][26][27][28]. Previous attempts to infect cell lines and primary cells from mice and rats in vitro were not successful [24].…”

“…Although primary cells and cell lines of these primates are susceptible to PERV infection in vitro [22][23][24], there is no evidence of a PERV transmission to these animals in vivo, even under conditions of immunosuppressive therapy and when high titers of virus are used [25][26][27]. Several attempts to establish a small animal model have failed [24,28].…”

Differences in Release and Determination of Subtype of Porcine Endogenous Retroviruses Produced by Stimulated Normal Pig Blood Cells

“…To date, only non-obese diabetic mice with severe combined immunodeficiency have been claimed to be infected with PERV in vivo by xenotransplanted pig islet cells [31,32]. Initial clinical and pre-clinical trials of xenotransplantation in humans, baboons and cynomolgus monkeys have been performed, but no evidence of infection with PERV was obtained [19,25,28,29,[33][34][35][36][37].…”

Monitoring for Presence of Potentially Xenotic Viruses in Recipients of Pig Islet Xenotransplantation

“…To date, more than 200 patients exposed to pig cells have been tested for evidence of PERV infection (3,5,14,15,16,17,21,24,26,27,33,34). Additionally, some 50 nonhuman primates have also been tested for PERV infection (20,32). No evidence of infection has been found.…”