Gene expression signatures in blood and muscle biopsy after intramuscular immunization of healthy adult humans with adjuvanted vaccines (BIOVACSAFE protocol 305E)
The gene expression in whole blood and simultaneous muscle biopsy (site of immunization and control contralateral non-injected leg) was measured in healthy adult male humans attending a research unit (CRC, University of Surrey, UK), who were randomized to receive a single immunization with an adjuvanted licensed vaccine or saline placebo control.
Overall design
Participants, all males, were randomized into the following groups (characteristics: treatment) to receive one of the following vaccines: FENDRIXE: intramuscular AS04C-alum-adjuvanted Fendrix, Hepatitis B (rDNA) vaccine (adjuvanted, adsorbed) supplied as a 0.5 mL suspension pre-filled syringe as a booster dose given to participants who were hepatitis B seropositive as a result of previous HBV immunization but negative for markers of HBV infection; FLUADE: intramuscular Fluad, MF59C-adjuvanted subunit vaccine supplied as a 0.5 ml pre-filled syringe containing influenza virus; PLACEBOE: intramuscular 0.5 mL normal saline. Participants attended on day 0 when pre-immunization baseline blood samples were drawn and vaccine or saline placebo intramuscularly administered into the anterolateral thigh of a designated leg (characteristics: injected side). The contralateral leg was not injected. The depth and angle of the injection was standardised and the injection site marked. Participants were randomized into groups (n = 5 per group) to undergo muscle biopsy and simultaneous blood draw on one of the following time points: 3 hours after immunization on day 0, days 1, 3, 5 or 7. For convenience a characteristics: hour value has been calculated for each array but this is only accurate at 0 and 3 hours, participants being free to attend at any time during the morning of the designated biopsy day after day 0. All whole blood samples were collected into PaxGene tubes. Muscle biopsies were obtained using an Abrahams suction / cutting needle under local anaesthetic. The needle was engraved at the same depth as the vaccine/placebo injection to facilitate accurate location of the injection site. A second biopsy was obtained from the same anatomical site in the contralateral non-injected control leg. Comments by the operator on the biopsy, quality, size, blood or adipose tissue presence have been included (characteristics: biopsy comments). A biopsy from the non-injected control leg was inadequate for RNA extraction in participant CRC305E9042 and so no array data are present. Biopsies were placed immediately into RNAlater for storage at 4°C overnight before freezing at -20°C and shipping on dry ice to the processing centre.
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