Varicella vaccination: evidence for frequent reactivation of the vaccine strain in healthy children.
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.
Krause
P R
PR
Laboratory of DNA Viruses, Bethesda, Maryland, USA.
Klinman
D M
DM
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002644:Chickenpox / Q000276:immunology / Q000517:prevention & control*; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006304:Health Status; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007223:Infant; D013045:Species Specificity; D014775:Virus Activation
D000914:Antibodies, Viral; D019433:Chickenpox Vaccine