Host SNPs and Altered Responses to Influenza Vaccine

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DESCRIPTION (provided by applicant): Inactivated influenza virus vaccines have been progressively improved over the past several decades to decrease reactogenicity and standardize antigenic content. Despite such progress, some otherwise healthy individuals either develop poor immune responses or experience adverse reactions to vaccination, strongly suggesting that host factors may play a role in determining responses to influenza vaccine. Various host immunogenetic polymorphisms are associated with host susceptibility and clinical manifestations of some infectious diseases, either by encoding altered gene products or by affecting transcriptional regulation. The present study will correlate polymorphisms of three host immunogenetic factors: the mannose binding lectin (MBL) gene, the tumor necrosis factor (TNF)-alpha and interleukin10 (IL-10) promoters, with host immune responses to inactivated influenza vaccines. Volunteers participating in previously conducted inactivated influenza vaccine trials who developed either decreased immune responses or increased adverse events to vaccination will be compared with those who developed brisk immune response and suffered no adverse events associated with vaccination. Subjects will be matched for age, gender and race. Genomic DNA will be extracted from frozen archived serum specimens obtained in a large previously conducted NIH-funded influenza vaccine field trial. The host polymorphisms in the MBL exon 1 genome and in the TNF-alpha and IL-10 promoter regions will be determined by PCR-based techniques. Defining host molecular determinants of influenza vaccine immunogenecity and adverse events may foster strategies to enhance vaccine effectiveness and safety in large patient populations. It is fully realized that the analysis of these three host polymorphisms may be too limited to pinpoint the genetic basis of variability in vaccine-induced responses, but the archived genomic DNA generated from the proposed studies will be used to examine additional, yet to be identified, host polymorphisms in the future.