No evidence of infectious retroviruses in measles virus vaccines produced in chicken embryo cell cultures

All vaccines that are prepared in chicken embryo fibroblasts (CEFs) contain a low level of particle-associated reverse transcriptase (RT) activity, wh ich is produced from the avian cell substrate. The RNAs present in the part icles have sequence homology to viral DNAs belonging to the ancient endogen ous avian virus (EAV) family or to the avian sarcoma-leukosis virus (ALV)-r elated subgroup E endogenous virus loci. Although no replication-competent retrovirus has been associated with the RT activity produced from CEFs, the re have been some theoretical safety concerns regarding potential consequen ces of integration of EAV and ALV sequences in human DNA, which may result from nonproductive infection with replication-defective particles or infect ion with EAV and ALV pseudotypes bearing measles virus envelopes. To addres s these possibilities, we have analyzed EAV and ALV particles in a measles virus vaccine equivalent (MVVE) preparation, obtained from a U.S. manufactu rer, for integration and for replication in human peripheral blood mononucl ear cells (PBMCs), The results show the absence of EAV and ALV integrants i n DNA prepared from MWE-inoculated human cells by direct DNA PCR and Alu PC R assays and no propagation of retrovirus in 18-day cultures of MVVE-inocul ated human PBMCs by a highly sensitive PCR-based RT assay. These results pr ovide further confidence regarding the safety of chicken RT activity in liv e viral vaccines and support the continued use of chick-cell-derived vaccin es in humans.