Prevalence of Antibodies against Adeno-Associated Viruses (AAVs) in Göttingen Minipigs and Its Implications for Gene Therapy and Xenotransplantation

Abstract

Adeno-associated viruses (AAV) are widely used as delivery vectors in clinical trials for in vivo gene therapy due to their unique features. Göttingen minipigs are a well-established animal model for several diseases and can be used for the efficacy and safety testing of AAV-based gene therapy. Pre-existing antibodies against AAV may influence the results of testing and, therefore, the animals should be tested for the presence of antibodies against relevant AAV serotypes. The detection of AAVs in pigs may be also important for the virus safety of xenotransplantation. In this study, we screened Göttingen minipigs from Ellegaard Göttingen Minipigs A/S, Denmark, and Marshall BioResources, USA, for antibodies against AAV1, AAV2, AAV6, AAV9 serotypes. Of the 20 animals tested, 18 had no neutralizing antibodies for all AAVs tested, none had antibodies against AAV9, only one had antibodies against AAV6, and the titers of antibodies against AAV1 and AAV2 were less than 1:100, with two exceptions. For total binding IgG, more individuals showed positivity for all the tested serotypes but, in general, the levels were low or zero. Three animals had no antibodies at all against the AAVs tested. Therefore, Göttingen minipigs could be considered an attractive animal model for gene therapy studies. Since some animals were negative for all AAVs tested, these may be selected and used as donor animals for xenotransplantation.