Clinical trial NCT03020498: B-cell Immunity to Influenza (SLVP017) - Years 2 (2010) & 3 (2011)
Official title: Protective Mechanisms Against a Pandemic Respiratory Virus. Project 1: B-cell Immunity to Influenza. Technical Development Project 1: Measuring the Immunome: Genomic Approaches to B-cell Repertoire - Years 2 (2010) & 3 (2011)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: Inactivated influenza vaccine
Live, attenuated influenza vaccine
Child identical twins and non-twins
Young and elderly non-twin adults
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2017-01-13
Enrollment: 91
Sex: ALL
Minimum age (years): 8
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: In this exploratory study, investigators will be looking at immune response differences between age groups and between the two different influenza vaccines given to identical twins, vaccine-naive young adults and elderly participants.

Detailed description: This is an exploratory study of healthy children and adults who are given either standard trivalent, inactivated influenza vaccine (TIV) or live, attenuated influenza vaccine (LAIV). There are no exclusions for gender, ethnicity or race. Following confirmation of written informed consent, baseline blood samples will be drawn from all study participants prior to immunization. The volunteers enrolled in any the three groups (A,B,C) cannot have been immunized with previous year's seasonal influenza vaccine. The identical twins in Groups A will be randomized to each receive a different vaccine (TIV or LAIV) than their twin. The non-twin children in Group B will also be randomly assigned to receive either TIV or LAIV. Non-twin elderly adults in Group C will be given standard TIV. All participants will receive a single dose of their assigned influenza vaccine, either by intramuscular (IM) injection (TIV) or intranasal application (LAIV).

Eligibility criteria: Inclusion Criteria:

1. Healthy, ambulatory 8-17 year old identical twins, 8-30 year old non-twins, or 70-100 year old elderly non-twin adults.
2. Willing to complete the informed consent process.
3. Availability for follow-up for the planned duration of the study at least 28 days after immunization.
4. Acceptable medical history by medical history and vital signs.

Exclusion Criteria:

1. Prior vaccination with seasonal TIV or LAIV or H1N1.
2. Prior off-study vaccination with the current seasonal TIV or LAIV
3. Allergy to egg or egg products, or to vaccine components
4. Life-threatening reactions to previous influenza vaccinations
5. Asthma or history of wheezing
6. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
7. History of immunodeficiency (including HIV infection)
8. 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.
9. Blood pressure \>150 systolic or \>95 diastolic at first study visit
10. Hospitalization in the past year for congestive heart failure or emphysema.
11. Chronic Hepatitis B or C.
12. Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in all groups; inhaled steroid use is not permissible except for non-LAIV Group C only). Use of oral steroids (\<20mg prednisone-equivalent/day) may be acceptable for volunteers 70-100 yrs of age after review by the investigator.
13. Participants in close contact with anyone who has a severely weakened immune system should not receive LAIV (Groups A and B only)
14. 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).
15. 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.
16. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
17. 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.
18. Receipt of blood or blood products within the past 6 months
19. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
20. Inactivated vaccine 14 days prior to vaccination
21. Live, attenuated vaccine within 60 days of vaccination
22. History of Guillain-Barré Syndrome
23. Pregnant or lactating woman
24. Use of investigational agents within 30 days prior to enrollment
25. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
26. 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 Who Received Influenza Vaccine
timeFrame: Day 0 to 28
Secondary outcomes:
measure: Number of Participants With Related Adverse Events
timeFrame: Day 0 to 28 post-immunization
Other outcomes:
measure: Investigate the Effects of Different Influenza Vaccines, Including Live Attenuated Vaccine (LAIV) and Inactivated Vaccine Delivered by Different Routes (Intranasal and IM), on B-cell Responses.
timeFrame: Day 0 to 28
Locations:
Study officials:
affiliation: Stanford University
name: Cornelia Dekker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Harry Greenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Stephen Quake, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Xiaosong He, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sasaki S, Holmes TH, Albrecht RA, Garcia-Sastre A, Dekker CL, He XS, Greenberg HB. Distinct cross-reactive B-cell responses to live attenuated and inactivated influenza vaccines. J Infect Dis. 2014 Sep 15;210(6):865-74. doi: 10.1093/infdis/jiu190. Epub 2014 Mar 27.
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: Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.
citation: de Bourcy CFA, Dekker CL, Davis MM, Nicolls MR, Quake SR. Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis. Sci Immunol. 2017 Sep 29;2(15):eaan8289. doi: 10.1126/sciimmunol.aan8289.