Clinical trial NCT02141581: Plasmablast Trafficking and Antibody Response in Influenza Vaccination (SLVP021 2011-2014)
Official title: Vaccination and Infection: Indicators of Immunological Health and Responsiveness. Project 1: Plasmablast Trafficking and Antibody Response in Influenza Vaccination;
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: Intramuscular inactivated trivalent influenza vaccine
Intradermal inactivated trivalent influenza vaccine
Live, attenuated influenza vaccine
Young adults
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2014-05-19
Enrollment: 86
Sex: ALL
Minimum age (years): 8
Maximum age (years): 34
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to investigate the responses to licensed trivalent, inactivated influenza vaccine (TIV) delivered by different routes: intramuscular (IM) and intradermal (ID) and to the live, attenuated influenza vaccine (LAIV) administered intranasally -- all given to generally healthy male and female adult volunteers.

Detailed description: The aim of this study is to compare the response to different formulations of licensed influenza vaccines.

The type of seasonal influenza vaccination(s) received independently by volunteers in the year(s) since their last study visit will not impact eligibility. Volunteers will be assigned into one of three vaccine groups (intramuscular trivalent inactivated influenza vaccine (TIV); live attenuated influenza vaccine (LAIV- given year 1 only) or intradermal TIV, based on the type of study vaccine they received in 2010, 2011, 2012, or 2013. All participants will receive a single dose of their assigned seasonal influenza vaccine. Volunteers will complete 3 study visits at Day 0, Day 6-8 and Day 24-32.

Eligibility criteria: Inclusion Criteria:

* Otherwise healthy, ambulatory between the ages of 8-33 years, inclusively.
* Willing to complete the informed consent process
* Availability for follow-up for the planned duration of the study at least 28 days after immunization
* Acceptable medical history and vital signs

Exclusion Criteria:

* Prior vaccination with seasonal TIV or LAIV
* Prior off-study vaccination with TIV or LAIV in the current flu season
* Allergy to egg or egg products, or to vaccine components 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
* Asthma or history of wheezing (for volunteers receiving LAIV only)
* Participants in close contact with anyone who has a severely weakened immune system should not receive LAIV (for volunteers receiving LAIV only)
* 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
* Chronic Hepatitis B or C
* Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays, inhaled steroids and topical steroids are permissible in both groups)
* 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. aspirin 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 or planned receipt of blood products prior to completion of study visits
* Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
* Inactivated vaccine 14 days prior to vaccination or planned non-study vaccination prior to completion of Visit 03 (\~Day 28 after the study vaccination)
* Live, attenuated vaccine within 60 days of vaccination or planned non-study vaccination prior to completion of Visit 03 (\~Day 28 after the study vaccination)
* Need an allergy immunization (that cannot be postponed) during the study period V01 to V03 (\~Day 28)
* History of Guillain-Barré Syndrome
* Pregnant or lactating woman
* Use of investigational agents within 30 days prior to enrollment or planned use of investigational agents prior to completion of study visits
* Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or planned blood donation prior to completion of study visits
* 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

Primary outcomes:
measure: Number of Participants From Each Arm Who Received Influenza Vaccine
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: Number of Participants With Related Adverse Events
timeFrame: Baseline to Day 28
Other outcomes:
measure: Frequency of Vaccine-specific Antibody Secreting Cells on Day 5 and Day 7 After Vaccination
timeFrame: Baseline to Day 7
Locations:
city: Stanford
country: United States
facility: Stanford LPCH Vaccine Program
state: California
Study officials:
affiliation: Stanford University
name: Cornelia L Dekker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Harry B Greenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Xiaosong He, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vollmers C, Sit RV, Weinstein JA, Dekker CL, Quake SR. Genetic measurement of memory B-cell recall using antibody repertoire sequencing. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13463-8. doi: 10.1073/pnas.1312146110. Epub 2013 Jul 29.
citation: He XS, Holmes TH, Sanyal M, Albrecht RA, Garcia-Sastre A, Dekker CL, Davis MM, Greenberg HB. Distinct patterns of B-cell activation and priming by natural influenza virus infection versus inactivated influenza vaccination. J Infect Dis. 2015 Apr 1;211(7):1051-9. doi: 10.1093/infdis/jiu580. Epub 2014 Oct 21.
citation: Le Gars M, Kay AW, Bayless NL, Aziz N, Dekker CL, Swan GE, Davis MM, Blish CA. Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy. J Infect Dis. 2016 Dec 1;214(11):1666-1671. doi: 10.1093/infdis/jiw448. Epub 2016 Sep 21.