Submitted to: Journal of Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 4/13/1999
Publication Date: N/A
Citation: Interpretive Summary: Embryonic chicken cells are used to prepare measles and mumps vaccines. Recently, a European-made measles vaccine tested positive for the presence of a protein termed reverse transcriptase (RT) which is specific for the presence of host-related endogenous genetic elements of avian retrovirus (EAV). This positive reactivity was shown to originate from the chicken cells used to prepare the vaccine, suggesting the presence of such EAV particles in the vaccine. Our investigation of RT activity in measles and mumps vaccines from a U.S. manufacturer also revealed positive reactivity for EAV. The positive reactivity was found in both chicken cells and the vaccines. However, no infectious (active) virus particles were detected in the material tested, indicating that this positive RT activity originated from incomplete, non-infectious EAV particles. Further, blood cells collected from 33 children that received the vaccines tested negative for any infectious avian retrovirus. The present data do not support transmission of avian retrovirus to recipients of the U.S.-made vaccines and provide reassurance for current immunization policies. This new information is significant to vaccine manufacturers, health officials as well as the general public.
Technical Abstract: Reverse transcriptase (RT) activity has been recently detected in all chicken cell-derived measles and mumps vaccines. A study of a vaccine manufactured in Europe indicated that the RT is associated with particles containing endogenous avian retrovirus (EAV-0) RNA and originates from the chicken embryonic fibroblasts (CEF) used as a substrate for propagation of the vaccine. We investigated the origin of RT in measles and mumps vaccines from a US manufacturer, and confirmed the presence of RT and EAV RNA. Additionally, we provide new evidence for the presence of avian leukosis virus (ALV) in both CEF supernatant and vaccines. ALV pol sequences were first identified in particle-associated RNA by amplification with degenerate retro viral pol primers. ALV RNA sequences from both the gag and env regions were also detected. Analysis of the hyper variable region 2 of env revealed subgroup E sequence, an endogenous type ALV. Both CEF- and vaccine-derived RT activity could be blocked by antibodies to ALV RT. Release of ALV-like particles from uninoculated CEF was also documented by electron microscopy. Nonetheless, infectivity studies on susceptible 15B1 chicken cells gave no evidence of infectious ALV, which is consistent with the phenotypes of the ev loci identified in the CEF. PCR analysis for ALV and EAV proviral sequences in peripheral blood mononuclear cells sampled from 33 children after measles and mumps vaccination yielded negative results.