M. Shahabuddin et al., No evidence of infectious retroviruses in measles virus vaccines produced in chicken embryo cell cultures, J CLIN MICR, 39(2), 2001, pp. 675-684
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.