Clinical trial NCT03028974: Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029)
Official title: Adaptive and Innate Immunity, Memory and Repertoire in Vaccination and Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: Inactivated influenza vaccine
Live, attenuated influenza vaccine
Young children
Adults
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2017-01-23
Enrollment: 77
Sex: ALL
Minimum age (years): 6
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to get a better understanding of the natural and adaptive immune response to the flu virus and to compare the immune cell responses to FDA-licensed flu vaccines in nasal mucosal cells and in blood.

Detailed description: This is a study of healthy children and adults receive the current seasonal influenza vaccine. The volunteers were enrolled into one of 7 groups over a 5-year period. Immunization is administered; blood samples and NP swabs are collected at various time points based on groups assigned.

Group A (LAIV4/annual return): Up to six 2-4 year old volunteers are given a quadrivalent live, attenuated influenza vaccine (LAIV4). All participants in this group are asked to return annually for flu immunization and blood samples on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a second immunization per standard of care. This group was discontinued in year 3 due to Advisory Committee on Immunization Practices (ACIP) recommendations against the use of LAIV.

Group B (LAIV4/ single year): Up to twenty 2-4 year old volunteers were given a quadrivalent live, attenuated influenza vaccine (LAIV4). Volunteers will participate for a single year. All participants in this group were immunized on Day 0. Blood samples were taken on on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a second immunization per standard of care. This group was discontinued in year 3 due to ACIP recommendations against the use of LAIV.

Group C (LAIV4/NP swab group): Up to twenty 2-4 year old volunteers were given a quadrivalent live, attenuated influenza vaccine (LAIV4). Nasopharyngeal samples (NP) swabs were collected Day 1 and 21 and 28 post immunization. No blood was collected for this group. Vaccine naive children returned 30 days later for a second immunization per standard of care. This group was discontinued in year 3 due to ACIP recommendations against the use of LAIV.

Group D (IIV4/annual return): Up to six 6 month-23 month old (inclusive) volunteers are given a quadrivalent inactivated influenza vaccine (IIV4). All participants in this group are asked to return annually for flu immunization and blood samples on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a second immunization per standard of care.

Group E (IIV4/single year): Up to twenty 6 month-23 month old (inclusive) volunteers were given a quadrivalent inactivated influenza vaccine (IIV4). Volunteers participate for a single year. All participants in this group were immunized on Day 0. Blood samples were taken on on Day 0 and Day 7 post immunization. Vaccine naive children returned 30 days later for a second immunization per standard of care.

Group F (LAIV4/single year) Up to forty 9-13 year old (n= 20) and 18-49 year old (n= 20) volunteers were given live, attenuated influenza vaccine (LAIV). Blood samples were collected Days 0, 7, and 28 and NP swabs were collected Days 1 and 28. This group was discontinued in year 3 due to ACIP recommendations against the use of LAIV.

Group G (IIV4/single year) Up to forty, 9-13 year old (n= 20) and 18-49 year old (n= 20) volunteers were given a quadrivalent inactivated influenza vaccine (IIV4). Blood samples were collected Day 0,7, and 28

Eligibility criteria: Inclusion Criteria:

1. Otherwise healthy, 6 mo-49 year-old volunteers.
2. Willing to complete the informed consent process (including assent for minors 7-17 years of age).
3. Availability for follow-up for the planned duration of the study.
4. For parents of children 6 months - 4 years of age: Willing to participate in the study annually for up to 5 years (if yes, consider for annual return groups).
5. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.
6. Influenza vaccine-naive or only one prior season of flu immunization with IIV (does not apply to Groups F and G).

Exclusion Criteria:

1. Prior off-study vaccination with the current year's seasonal influenza vaccine
2. Receipt of LAIV in the prior season (does not apply to Groups F and G)
3. Received flu immunizations in 2 or more prior flu seasons (does not apply to Groups F and G)
4. Allergy to egg or egg products, or to vaccine components, (including gentamicin, gelatin, arginine or MSG if given LAIV4)
5. Life-threatening reactions to previous influenza vaccinations
6. Asthma in adults. Children aged 2 through 4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months, or for whom parents report that a health care provider stated that they had wheezing or asthma within the last 12 months \[If yes, not eligible for LAIV Groups A, B, C, \& F\].
7. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
8. History of immunodeficiency (including HIV infection)
9. For children or adolescents through 17 years of age,receiving aspirin therapy or aspirin-containing products \[If yes, not eligible for LAIV Groups A, B, C, and F\].
10. 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.
11. Blood pressure \>150 systolic or \>95 diastolic at first study visit and the day of vaccination (for children 12 yrs and older, and adults).
12. Hospitalization in the past year for congestive heart failure or emphysema.
13. Chronic Hepatitis B or C
14. 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)
15. Participants in close contact with anyone who has a severely weakened immune system and requires a protective environment. Exposure to such persons should be avoided for 7 days after receipt of LAIV. \[If yes, may be ineligible for Groups A,B, C and F\].
16. 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).
17. 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
18. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
19. 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.
20. Has taken an influenza antiviral medication within 48 hours prior to study vaccination \[If yes, not eligible for LAIV Groups A, B, C and F\].
21. Receipt of blood or blood products within the past 6 months or planned used during the study
22. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol.
23. Receipt of inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit
24. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit
25. Need for allergy immunization (that cannot be postponed) during the study period
26. History of Guillain-Barre syndrome
27. Pregnant woman
28. Breastfeeding \[If yes, not eligible for LAIV Group F\]
29. Use of investigational agents within 30 days prior to enrollment or planned use during the study
30. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or planned donation prior to completion of the last visit
31. 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: Count of Participants From Each Arm Who Received Influenza Vaccine
timeFrame: Day 0 to 28-32 post immunization
Secondary outcomes:
measure: Count of Participants With Related Adverse Events
timeFrame: Day 0 to 28-32 post-immunization
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
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: Xiaosong He, PhD
role: PRINCIPAL_INVESTIGATOR
References: