Lack of Cross-Species Transmission of Porcine Endogenous Retrovirus in Pig-to-Baboon Xenotransplantation with Sustained Depletion of Anti-??Gal Antibodies

Abstract

Background. Nonhuman primates are potential permissive animals for studying the risk of in vivo infection with porcine endogenous retrovirus (PERV). Anti-αGal natural antibodies are considered one of the barriers for preventing PERV infection, and it has been postulated that reduction of these antibodies could increase the risk of this infection. The aim of this study was to investigate the role of GAS 914, which depletes anti-αGal antibodies, in the potential in vivo transfer of PERV after pig-to-baboon organ xenotransplantation. Methods. Twenty-seven baboons underwent xenotransplantation with hDAF or hMCP/hDAF transgenic pig organs, including heterotopic heart (n=14) and kidney (n=13) transplants. All of them received GAS 914 along with different immunosuppression protocols. PERV sequences were investigated by reverse-transcriptase polymerase chain reaction and by polymerase chain reaction assays in samples obtained at autopsy. The presence of PERV-specific antibodies and/or pig xenomicrochimerism was also evaluated. Results. PERV RNA was not detected in any baboon plasma sample. In addition, all plasma samples were negative for PERV antibodies. However, PERV DNA sequences were detected in peripheral blood mononuclear cells from 6 of 14 (43%) animals investigated. Porcine mitochondrial DNA was also found in all of these positive samples and in six of the eight (75%) samples with negative PERV DNA, indicating that the detection of PERV sequences was attributable to xenochimerism. PERV-positive cells as a result of xenochimerism were also found in eight of nine (89%) spleen and lymph node tissue samples tested. Conclusions. Sustained depletion of anti-αGal antibodies does not augment the risk of PERV infection in pig-to-baboon organ transplantation.