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

Abstract

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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Acknowledgements

We thank P., Patriarca, A., Rosenberg, F., Steinberg and W., Egan for their critical review of this manuscript. We also thank M. Gesemann for providing raw data from a 4-year follow-up of recipients of hepatitis B vaccine. The assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Food and Drug Administration.

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Correspondence to Philip R. Krause.

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Figure 1: Antibody titers were obtained from seronegative vaccinees 6 weeks after immunization and yearly thereafter.