Evaluation of Vero-cell-derived simian endogenous retrovirus infection in humans by detection of viral genome in clinicopathological samples and commercialized vaccines and by serology of Japanese general population.
Vero cells are used in laboratories for the isolation of viruses and the production of vaccines. Recently, the sequence of simian endogenous retrovirus (SERV) was identified in Vero cells (SERVagm-Vero), with homology to exogenously transmitted, pathogenic simian retroviruses (SRVs). Although SERVagm-Vero was shown to be noninfectious to human cells in vitro, SERV infection in humans is controversial. In this study, we evaluated the status of SERV infection in humans by detecting the viral genome in clinicopathological samples and commercialized vaccines, and with a serological survey of the Japanese general population.



Real-time polymerase chain reaction (PCR) and reverse transcription-PCR were used to detect the SERVagm-Vero genome. We also examined the seroprevalence of SERV in 1000 individuals in the Japanese population with an enzyme-linked immunoabsorbent assay (ELISA) using mixed SERVagm-Vero gag, pol, and env proteins as antigens.



Real-time PCR failed to detect SERVagm-Vero genomic fragments in 783 human clinicopathological samples, and all 13 human cell lines tested were negative for the SERVagm-Vero genome. Thirteen commercialized vaccines, including five Vero-based vaccines, were also negative for the SERVagm-Vero genome on real-time PCR and reverse transcription-PCR. Eight (0.8%) were seropositive on ELISA, and western blotting showed that all eight sera contained anti-pol antibodies. All SERV-seropositive individuals were born before 1965, suggesting that SERV infection in Japan might not be associated with vaccine, because more than 90% of Japanese children born from 1964 to 2012 have received live poliovirus vaccines containing virus produced in Vero cells since the 1980s.



We have confirmed that the vaccines we use today are free of SERVagm-Vero. Moreover, SERV infection in humans is very rare and unlikely to be associated with vaccines in the Japanese general population.
Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Dermatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Hitomi
H
Fukumoto
Department of Pathology, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan.
Tsunekazu
T
Hishima
Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Hideki
H
Hasegawa
Department of Dermatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Hidehisa
H
Saeki
Pathogen Genomic Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Makoto
M
Kuroda
Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Electronic address: katano@nih.go.jp.
Harutaka
H
Katano
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D004340:Drug Contamination; D020077:Endogenous Retroviruses / Q000302:isolation & purification*; D016679:Genome, Viral; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008875:Middle Aged; D015301:Retroviruses, Simian / Q000302:isolation & purification*; D016036:Seroepidemiologic Studies; D014709:Vero Cells / Q000821:virology*; D014765:Viral Vaccines / Q000032:analysis*; D055815:Young Adult
D000914:Antibodies, Viral; D014765:Viral Vaccines
Real-time PCR; Seroprevalence; Simian endogenous retrovirus; Simian retrovirus; Vero