Genetic Measurement of Memory B-cell Recall Using Antibody Repertoire Sequencing

We developed an improved high throughput sequencing approach to measure the quantities and sequences of the repertoire of antibody heavy chain RNA in a blood sample. Using this approach we analyzed the antibody repertoire in response to yearly vaccinations with influenza vaccines TIV and LAIV in healthy adults in two subsequent years. We determined vaccine response patterns specific to LAIV and TIV and found antibody sequences that were shared between two samples of the same individuals following influenza vaccination in subsequent years, thereby providing a genetic measurement of B-cell memory recall.]]>
Subject Inclusion Criteria Otherwise healthy, 18-30 year old young adult. Acceptable medical history by medical history and vital signs. Subject Exclusion Criteria Prior vaccination with 2010-2011 seasonal TIV or LAIV. Prior off-study vaccination with the current 2011-2012 seasonal TIV or LAIV. Weight less than 110 pounds. Allergy to egg or egg products, or to vaccine components, including gelatin, or thimerosal (TIV multidose vials only). Life-threatening reactions to previous influenza vaccinations. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination. History of immunodeficiency (including HIV infection). Known or suspected impairment of immunologic function, including, but not limited to, clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease, or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol. Blood pressure >150 systolic or >95 diastolic at first study visit. Hospitalization in the past year for congestive heart failure or emphysema. Chronic Hepatitis B or C. Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible; after review by the investigator. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia). Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety. Receipt of blood or blood products within the past 6 months. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol. Receipt of inactivated vaccine 14 days prior to enrollment (14 days prior to vaccination) and within 28 days after vaccination. Live, attenuated vaccine within 55 days of enrollment (60 days of vaccination). History of Guillain-Barré Syndrome. Pregnant or lactating woman. Use of investigational agents within 30 days prior to enrollment. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment. Needs f/u. A member of the study team or their family member, to include investigators, research laboratory staff, clinical research staff. Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol. ]]>