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

Nat Med. 2000 Apr;6(4):451-4. doi: 10.1038/74715.


Wild-type varicella zoster virus (VZV) causes chickenpox, a common childhood illness characterized by fever and a vesicular rash and rare serious complications. Wild-type VZV persists in a latent form in the sensory ganglia, and can re-activate to cause herpes zoster. 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 community. 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.

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Chickenpox / immunology
  • Chickenpox / prevention & control*
  • Chickenpox Vaccine / administration & dosage
  • Chickenpox Vaccine / adverse effects*
  • Chickenpox Vaccine / immunology
  • Child
  • Child, Preschool
  • Health Status
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 3, Human / physiology*
  • Humans
  • Infant
  • Species Specificity
  • Virus Activation*


  • Antibodies, Viral
  • Chickenpox Vaccine