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A Role for Genetics in the Immune Response to the Varicella Vaccine

Klein, Nicola P. MD, PhD*†; Fireman, Bruce MA*; Enright, Andrea MD; Ray, Paula MPH*; Black, Steven MD*; Dekker, Cornelia L. MDfor the Clinical Immunization Safety Assessment (CISA) Network

The Pediatric Infectious Disease Journal: April 2007 - Volume 26 - Issue 4 - p 300-305
doi: 10.1097/01.inf.0000257454.74513.07
Original Studies

Background: A wide range in antibody titers has been found after immunization with the varicella vaccine, although the basis for these differences has not been described.

Methods: To evaluate the contribution of a genetic component in the immune response to the varicella vaccine, concordance for six-week postimmunization antibody titers was evaluated among 248 biologic siblings who participated in varicella vaccine clinical trials by comparing all pairs of siblings (151 pairs) to all possible unrelated, nonsibling pairs created from within this same cohort (30,477 pairs).

Results: Postimmunization antibody titers after 1 varicella vaccine dose were within the range observed historically among healthy vaccinees, with 85.4% of subjects having antibody responses greater than the approximate correlate of protection of 5 gpELISA units. Postimmunization antibody titers within sibling pairs clustered together more than or less than 10 gpELISA units when compared with within nonsibling pairs (P < 0.0001). Postimmunization titers within sibling pairs were also quantitatively closer together than were those within unrelated, nonsibling pairs (P = 0.022). The age-adjusted intraclass correlation coefficient indicated that the heritability of the varicella vaccine immune response is 45% (95% confidence interval of 15–75%).

Conclusions: Similarities in siblings' response to varicella vaccine are supportive of the hypothesis that genetic factors play a role in the antibody response to the varicella vaccine.

From the *Kaiser Permanente Vaccine Study Center and Division of Research, Oakland, CA; and the †Division of Pediatric Infectious Diseases, Lucile Packard Children's Hospital at Stanford and Stanford University School of Medicine, Stanford, CA.

Accepted for publication December 19, 2006.

Andrea Enright's current address is Department of Pediatrics, Palo Alto Medical Foundation, Palo Alto, CA.

Address for correspondence: Nicola P. Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th floor, Oakland, CA 94612. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.