Inverse relationship between six week postvaccination varicella antibody response to vaccine and likelihood of long term breakthrough infection.
BACKGROUND
We used the large clinical database that supported the development of Oka/ Merck varicella vaccine to study the relationship between the primary varicella antibody response, as determined by gpELISA, an enzyme-linked immunosorbent assay that detects antibodies to varicella-zoster virus (VZV) glycoprotein, and the subsequent risk of postvaccination breakthrough varicella.


METHODS
We vaccinated 1,164 healthy children with a single dose of varicella vaccine containing 2900 to 9000 plaque-forming units/dose. The primary immune response to vaccination was determined by gpELISA 6 weeks after vaccination. Subjects were followed annually for 7 years to ascertain cases of breakthrough varicella.


RESULTS
The estimated vaccine efficacy among children with a 6-week postvaccination antibody titer of > or = 5 gpELISA units was 95.5% (95% confidence interval, 94.2%, 96.8%) compared with 83.5% (95% confidence interval, 76.9%, 89.5%) for subjects with a titer of <5 gpELISA units. Children with a 6-week postvaccination antibody titer of <5 gpELISA units were 3.5 times more likely than those with a titer of > or = 5 gpELISA units to develop breakthrough varicella.


CONCLUSIONS
We identified a 6-week postvaccination antibody titer of > or = 5 gpELISA units as an approximate correlate of protection. In addition we established an accelerated failure time model based on log normal hazard that predicted varicella breakthrough rates based on the distribution of 6-week postvaccination varicella antibody titers.
Li
Shu
S
Merck Research Laboratories, Merck & Co, Inc, West Point, PA 19486, USA.
Chan
Ivan S F
IS
Matthews
Holly
H
Heyse
Joseph F
JF
Chan
Christina Y
CY
Kuter
Barbara J
BJ
Kaplan
Karen M
KM
Vessey
S J Rupert
SJ
Sadoff
Jerald C
JC
D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation; D002644:Chickenpox / Q000276:immunology* / Q000473:pathology; D019433:Chickenpox Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors
D000914:Antibodies, Viral; D019433:Chickenpox Vaccine