Innate and Acquired Immunity to Influenza Infection and Immunization (SLVP029)

Adaptive and Innate Immunity, Memory and Repertoire in Vaccination and Infection

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: FluMist®; Biological: Fluzone®

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

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 49 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A: 2-4 yo LAIV4 (Return); Participants are given quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® . For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1. All participants in this group will be asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.	Biological: FluMist®; FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray
Other: Group B: 2-4 yo LAIV4 (Single Yr); Participants are given LAIV4/ FluMist® and participate for single year. For children requiring 2 doses of vaccine, a second immunization will be given at Day 28-32 after Dose 1.	Biological: FluMist®; FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray
Other: Group C: 2-4 yo LAIV4 (Swab/Single Yr); Participants are given LAIV4/ FluMist® and participate for single year. NP swabs are collected; no blood samples will be collected for this group. For children requiring 2 doses of vaccine, a second immunization will be given at least 28 days after Dose 1.	Biological: FluMist®; FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray
Other: Group D: 6 - 23 mos old IIV4 (Return); Participants are given a quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® . For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1. Participants are asked to return annually for repeat immunization per ACIP guidelines and blood sample collection.	Biological: Fluzone®; Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine
Other: Group E: 6 - 23 mos old IIV4 (Single Yr); Participants are given IIV4/ Fluzone® and participate for a single year. For children requiring 2 doses of vaccine (vaccine-naïve), a second immunization will be given at Day 28-32 after Dose 1.	Biological: Fluzone®; Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine
Other: Group F: 9-13/18-49 yo LAIV4 (Single Yr); Participants 9-13 year old and 18-49 year old are given LAIV4/ FluMist® . Participants will participate for a single year.	Biological: FluMist®; FluMist® Quadrivalent: Quadrivalent influenza virus vaccine live, intranasal spray
Other: Group G: 9-13/18-49 yo IIV4 (Single Yr); Participants 9-13 year old and 18-49 year old are given IIV4/ Fluzone® and participate for single year.	Biological: Fluzone®; Fluzone® Quadrivalent: Quadrivalent influenza virus vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Count of Participants From Each Arm Who Received Influenza Vaccine	Day 0 to 28-32 post immunization

Secondary Outcome Measures

Outcome Measure	Time Frame
Count of Participants With Related Adverse Events	Day 0 to 28-32 post-immunization

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2014
• Primary Completion (Actual): November 20, 2017
• Study Completion (Actual): November 20, 2017

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 19, 2017
• First Posted (Estimate): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Adults; Young children; Live, attenuated influenza vaccine; Inactivated influenza vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: SU-31136-2014-2019; U19AI057229-11 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO