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Article
Nature Medicine  6, 451 - 454 (2000)
doi:10.1038/74715

Varicella vaccination: Evidence for frequent reactivation of the vaccine strain in healthy children

Philip R. Krause1 & Dennis M. Klinman2

1  Laboratory of DNA Viruses

2  Section of Retroviral Research, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Bethesda, Maryland 20892, USA

Correspondence should be addressed to Philip R. Krause krause@cber.fda.gov
Wild-type varicella zoster virus (VZV) causes chickenpox, a common childhood illness characterized by fever and a vesicular rash1 and rare serious complications2. Wild-type VZV persists in a latent form in the sensory ganglia, and can re-activate to cause herpes zoster3. More than 10 million American children have received the live attenuated Oka strain VZV vaccine (OkaVZV) since its licensure in 1995. Pre-licensure clinical studies showed that mean serum anti-VZV levels among vaccinees continued to increase with time after vaccination. This was attributed to immunologic boosting caused by exposure to wild-type VZV in the community4, 5. Here, we examine the alternative, that large-scale asymptomatic reactivation of OkaVZV might occur in vaccinees. We analyzed serum antibody levels and infection rates for 4 years of follow-up in 4,631 children immunized with OkaVZV. Anti-VZV titers decreased over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical infection and immunological boosting substantially exceeded the 13%-per-year rate of exposure to wild-type varicella. These findings indicate that OkaVZV persisted in vivo and reactivated as serum antibody titers decreased after vaccination. This has salient consequences for individuals immunized with OkaVZV.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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