Plasmablast Trafficking and Antibody Response in Influenza Vaccination (SLVP021 2011-2014)

Vaccination and Infection: Indicators of Immunological Health and Responsiveness. Project 1: Plasmablast Trafficking and Antibody Response in Influenza Vaccination;

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluzone® (IM); Biological: Fluzone® Intradermal (ID); Biological: 2011-2012 FluMist®

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.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford LPCH Vaccine Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 34 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A Fluzone® (IM); Participants in this group will be randomized to the trivalent inactivated influenza vaccine (TIV), Fluzone®, administered intramuscularly (IM) 2011-2012, 2012-2013 or 2013-2014 Fluzone was used as appropriate for the current year of study	Biological: Fluzone® (IM); This vaccine is given intramuscularly (IM); Other Names: FDA-licensed seasonal influenza vaccine; Trivalent inactivated influenza vaccine (TIV)
EXPERIMENTAL: Group B Fluzone® Intradermal (ID); Participants in this group will be randomized to the trivalent inactivated influenza vaccine (TIV), Fluzone® Intradermal, administered intradermally (ID) 2011-2012, 2012-2013 or 2013-2014 Fluzone Intradermal was used as appropriate for the current year of study	Biological: Fluzone® Intradermal (ID); This vaccine is given intradermally (ID); Other Names: Trivalent inactivated influenza vaccine (TIV); FDA-licensed seasonal Influenza Vaccine
EXPERIMENTAL: Group C 2011-2012 FluMist®; Participants in this group will be randomized to 2011-2012 live attenuated influenza vaccine, FluMist®, administered intranasally. FluMist was only used in the first year of study.	Biological: 2011-2012 FluMist®; This vaccine is given intranasally; Other Names: FDA-licensed seasonal influenza vaccine; Live, attenuated influenza vaccine (LAIV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants From Each Arm Who Received Influenza Vaccine	Baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Related Adverse Events	Number of participants with Related Adverse Events with a 0% Frequency Threshold	Baseline to Day 28

Other Outcome Measures

Outcome Measure	Time Frame
Frequency of Vaccine-specific Antibody Secreting Cells on Day 5 and Day 7 After Vaccination	Baseline to Day 7

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Stanford-LPCH Vaccine Program clinical trial website

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: May 15, 2014
• First Submitted That Met QC Criteria: May 16, 2014
• First Posted (ESTIMATE): May 19, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2018
• Last Update Submitted That Met QC Criteria: April 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Young adults; Live, attenuated influenza vaccine; Intramuscular inactivated trivalent influenza vaccine; Intradermal inactivated trivalent influenza vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: SU-21987- 2011; 1U19AI090019-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The NIH Human Immunology Project Consortium (HIPC) data repositories (ImmPORT) may store the results of the research assays results. Genetic data that is developed in this study may be made available to other researchers through the National Center for Biotechnology Information (NCBI) databases. Results from research assays will be labeled with a unique ID code and the volunteer identity (except for age) will not be disclosed.