Atopy history and the genomics of wheezing after influenza vaccination in children 6-59 months of age

Background: A multinational clinical trial compared the safety and efficacy of intranasal trivalent live attenuated influenza vaccine (LAIV) with intramuscular trivalent inactivated vaccine (TIV) in very young children prior to the 2004-5 influenza season [1]. Wheezing was noted more often in recipients of LAIV and laboratory-confirmed influenza infection was noted more often in recipients of TIV. We sought to determine whether epidemiologic or genetic factors were associated with these outcomes. Methods: Atopy surveys and DNA collections were performed in trial participants at two United States sites, Nashville, TN and Boston, MA. DNA samples were genotyped on Illumina lnfinium 610 or 660-Quad. Standard allelic tests of association were performed. Results: At the Nashville and Boston sites, a total of 99 children completed the trial, 6 (1 TIV, 5 LAIV) developed medically attended wheezing within 42 days following vaccination, and 8 (5 TIV, 3 LAIV) developed laboratory-confirmed influenza during the season. Eighty-one surveys and 70 DNA samples were collected. Family history of asthma (p = 0.001) was associated with wheezing after vaccination. Of 468,458 single nucleotide polymorphisms tested in the genome-wide association study (GWAS), none achieved genome-wide significance for either wheezing after vaccination or laboratory-confirmed influenza infection. Conclusions: Family history of asthma appears to be a risk factor for wheezing after influenza vaccination. Given the limitations of the sample size, our pilot study demonstrated the feasibility of performing a GWAS but was not able to determine genetic polymorphisms associated with wheezing after influenza immunization. (C) 2011 Elsevier Ltd. All rights reserved.