Transcriptional profiling of HBV-naïve subjects before vaccination against Hepatitis A/B viruses, Diphtheria/Tetanus toxoids and Cholera.. Homo sapiens

Mechanisms of poor responses to vaccines remain unknown. Hepatitis B virus-naïve elderly subjects received three vaccines, including a vaccine against hepatitis B virus (HBV). Pre-vaccination high dimensional analyses of blood using transcriptional profiling and flow cytometry revealed that subjects having increased memory B cell frequencies and higher expression of genes downstream of B cell receptor signaling responded more strongly to the HBV vaccine whereas subjects having higher expression of inflammatory related genes and greater numbers of activated innate immune cells showed a weaker response to this vaccine. The heme-induced response was associated with the poor response to the hepatitis B vaccine. Transcriptional profiling and flow cytometry results were validated in a distinct set of elderly subjects with accuracy greater than 60%. Our study is the first that identifies baseline predictors of responses to vaccines in a population of subjects known to be highly susceptible to infections. Overall design: One hundred and seventy four (174) generally healthy, Hepatitis B virus (HBV) naïve, adult residents of Québec were vaccinated with two doses of Twinrix® (HBsAg and Hepatitis A virus - Glaxo Smith-Kline), generic Tetanus-diphtheria booster (tetanus and diphtheria - Sanofi-Pasteur), and Dukoral (recombinant cholera toxin B subunit and whole killed Vibrios - Sanofi Pasteur) according to the respective product labels. Blood samples were taken immediately prior to vaccination. Blood samples were conserved in PAXgene tubes. RNA was extracted and hybridized to Affymetrix arrays. 5 technical replicates were included in the study.