Evidence of avian leukosis virus subgroup E and endogenous avian virus in measles and mumps vaccines derived from chicken cells: Investigation of transmission to vaccine recipients

Reverse transcriptase (RT) activity has been detected recently in all chick en cell-derived measles and mumps vaccines. A study of a vaccine manufactur ed in Europe indicated that the RT is associated with particles containing endogenous avian retrovirus (EAV-0) RNA and originates from the chicken emb ryonic fibroblasts (CEF) used as a substrate for propagation of the vaccine . We investigated the origin of RT in measles and mumps vaccines from a U.S . manufacturer and confirm the presence of RT and EAV RNA. Additionally, we provide new evidence for the presence of avian leukosis virus (ALV) in bot h CEF supernatants and vaccines. ALV pol sequences were first identified in particle-associated RNA by amplification with degenerate retroviral pal pr imers. ALV RNA sequences from bath the gag and Env regions were also detect ed. Analysis of hypervariable region 2 of env revealed a subgroup E sequenc e, an endogenous-type ALV. Both CEF- and vaccine-derived RT activity could be blocked by antibodies to ALV RT. Release of ALV-like virus particles fro m uninoculated CEF was also documented by electron microscopy. Nonetheless, infectivity studies on susceptible 15B(1) chicken cells gave no evidence o f infectious ALV,which is consistent with the phenotypes of the ev loci ide ntified in the CEF. PCR analysis of ALV and EAV proviral sequences in perip heral blood mononuclear cells from 33 children after measles and mumps vacc ination yielded negative results. Our data indicate that the sources of RT activity in all RT-positive measles and mumps vaccines may not be similar a nd depend on the particular endogenous retroviral loci present in the chick en cell substrate used. The present data do not support transmission of eit her ALV or EAV to recipients of the U.S.-made vaccine and provide reassuran ce for current immunization policies.