Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

NCT ID: NCT01246999

Last Updated: 2016-12-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

A total of 88 children between 2 and 9 years of age will be randomized to receive a two dose schedule of either licensed live attenuated trivalent seasonal influenza vaccine (LAIV) or licensed inactivated seasonal influenza vaccine (TIV)or TIV followed by LAIV or LAIV followed by TIV separated by 28 days. Children with a laboratory documented history of prior H1N1 infection will be excluded.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The study will be conducted as a randomized, prospective, open-label evaluation of the clinical tolerability, vaccine virus shedding, and serum and mucosal antibody response to vaccination with either live trivalent influenza vaccine (LAIV) or trivalent influenza vaccine (TIV) in healthy children between the ages of 2 and 9 years. Children will be screened for antibody to A/Brisbane/57/07 (H1N1) and A/California/07/09 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 before and at indicated times after the start of the study. They will not be randomized based on antibody levels. Children with prior documented infection with the 2009 pandemic H1N1 virus will be excluded. Vaccine will be administered on days 0 and 28.

Safety of vaccination will be assessed using symptoms collected by parents for 7 days after each dose of vaccine. Serum will be obtained prior to and on day 28 following each dose of vaccine and assessed for antibody by HAI, ELISA, and neutralization techniques. Nasal secretions will be obtained by nasal wick prior to and on day 28 after each dose and assessed for HA-specific IgA (immune globulin A) and IgG (immune globulin G)antibody by ELISA. Nasal swabs will be obtained on days 2, 4, and 7 after each dose of live vaccine and assessed for the presence and magnitude of vaccine virus shedding of the live attenuated vaccine by rtRT-PCR (real-time reverse transcriptase polymerase chain reaction)and TCID50 (50% tissue culture infectious doses)on MDCK(Madin Darby Canine Kidney) cells.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Influenza

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Influenza A/California/7/2009-like (2009 H1N1) A/Perth/16/2009-like (H3N2) B/Brisbane/60/2008-like (B/Victoria lineage)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Live Attenuated Influenza vaccine

LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later

Group Type ACTIVE_COMPARATOR

Live attenuated Influenza vaccine

Intervention Type BIOLOGICAL

0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days

Trivalent Influenza Vaccine 2010-2011

TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 8 years intramuscularly followed by a second dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly 28 days later

Group Type ACTIVE_COMPARATOR

Trivalent Influenza Vaccine

Intervention Type BIOLOGICAL

.25 mL given intramuscularly to children 24 to 36 months of age, 2 doses given 28 days apart, .5 mL given intramuscularly to children 37 months to 9 years of age, 2 doses given 28 day s apart.

TIV followed by LAIV

TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later

Group Type ACTIVE_COMPARATOR

TIV followed by LAIV

Intervention Type BIOLOGICAL

TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later

LAIV followed by TIV

LAIV will be given in a dose of .2 ml intranasally followed by a dose of TIV given in a dose of .25 ml 2 years to 36 months or .5 ml 37 months to 9 years intramuscularly 28 days later

Group Type ACTIVE_COMPARATOR

LAIV followed by TIV

Intervention Type BIOLOGICAL

LAIV .2 mL given through nasal spray (.1 mL in each nostril) Followed by TIV .25 mL given intramuscularly to children 24 to 25 months of age or .5 mL given intramuscularly to children 36 months to 9 years of age 28 days later

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Live attenuated Influenza vaccine

0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days

Intervention Type BIOLOGICAL

Trivalent Influenza Vaccine

.25 mL given intramuscularly to children 24 to 36 months of age, 2 doses given 28 days apart, .5 mL given intramuscularly to children 37 months to 9 years of age, 2 doses given 28 day s apart.

Intervention Type BIOLOGICAL

TIV followed by LAIV

TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later

Intervention Type BIOLOGICAL

LAIV followed by TIV

LAIV .2 mL given through nasal spray (.1 mL in each nostril) Followed by TIV .25 mL given intramuscularly to children 24 to 25 months of age or .5 mL given intramuscularly to children 36 months to 9 years of age 28 days later

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

FluMist Seasonal Influenza Vaccine Seasonal Influenza Vaccines Seasonal Influenza Vaccines

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Aged between 2 and 9 years, inclusive.
* No prior history of laboratory documented infection with novel H1N1 virus
* The subject must be in good health, as determined by: vital signs (heart rate \<140 bpm; blood pressure: systolic ≥ 90 mm Hg and ≤140 mm Hg; diastolic ≤ 90 mm Hg; oral temperature \<100.0ºF (fahrenheit); medical history; and targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months.
* The subject/parents are able to understand and comply with the planned study procedures, including being available for all study visits.
* The subject/parents have provided informed consent prior to any study procedures. (An assent will be obtained for all children as required by the institutional IRB (Institutional Review Board.)

Exclusion Criteria

* Subjects with a laboratory documented history of previous novel H1N1 infection.
* History of egg allergy or allergy to other components of vaccine.
* History of wheezing.
* The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy.
* The subject has an active neoplastic disease.
* The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (\>800 mg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).
* The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study.
* The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days (or 56 days for vaccine naïve recipients).
* The subject has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include chronic conditions recognized as risk factors for influenza complications or as contraindications for live vaccination, including chronic cardiac (exclusive of hypertension) or pulmonary conditions (including asthma), diabetes mellitus, or renal impairment.
* The subject has an acute illness or an oral temperature greater than 99.9 degreesF (37.7 degrees C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolve \> 3 days prior to enrollment.
* The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period.
* The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
* The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection.
* The subject has a previous history of Guillain-Barré syndrome within 6 weeks of receipt of influenza vaccination.
* The subject has any condition that the principal investigator (PI) believes may interfere with successful completion of the study.
Minimum Eligible Age

2 Years

Maximum Eligible Age

9 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role collaborator

University of Rochester

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

John Treanor

M.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

John J. Treanor, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Vaccine Research Unit Room 3-5000

Rochester, New York, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009 Nov 12;361(20):1945-52. doi: 10.1056/NEJMoa0906453. Epub 2009 Sep 10.

Reference Type BACKGROUND
PMID: 19745214 (View on PubMed)

Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, Lindstrom S, Gubareva LV, Deyde V, Garten RJ, Harris M, Gerber S, Vagasky S, Smith F, Pascoe N, Martin K, Dufficy D, Ritger K, Conover C, Quinlisk P, Klimov A, Bresee JS, Finelli L. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med. 2009 Jun 18;360(25):2616-25. doi: 10.1056/NEJMoa0903812. Epub 2009 May 7.

Reference Type BACKGROUND
PMID: 19423871 (View on PubMed)

Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, Basser RL. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med. 2009 Dec 17;361(25):2405-13. doi: 10.1056/NEJMoa0907413. Epub 2009 Sep 10.

Reference Type BACKGROUND
PMID: 19745216 (View on PubMed)

Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, Kemble G, Connor EM; CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007 Feb 15;356(7):685-96. doi: 10.1056/NEJMoa065368.

Reference Type BACKGROUND
PMID: 17301299 (View on PubMed)

Maassab HF. Biologic and immunologic characteristics of cold-adapted influenza virus. J Immunol. 1969 Mar;102(3):728-32. No abstract available.

Reference Type BACKGROUND
PMID: 5773321 (View on PubMed)

Chanock RM, Murphy BR. Use of temperature-sensitive and cold-adapted mutant viruses in immunoprophylaxis of acute respiratory tract disease. Rev Infect Dis. 1980 May-Jun;2(3):421-32. doi: 10.1093/clinids/2.3.421.

Reference Type BACKGROUND
PMID: 6997969 (View on PubMed)

Boyce TG, Gruber WC, Coleman-Dockery SD, Sannella EC, Reed GW, Wolff M, Wright PF. Mucosal immune response to trivalent live attenuated intranasal influenza vaccine in children. Vaccine. 1999 Aug 20;18(1-2):82-8. doi: 10.1016/s0264-410x(99)00183-8.

Reference Type BACKGROUND
PMID: 10501238 (View on PubMed)

Sasaki S, Jaimes MC, Holmes TH, Dekker CL, Mahmood K, Kemble GW, Arvin AM, Greenberg HB. Comparison of the influenza virus-specific effector and memory B-cell responses to immunization of children and adults with live attenuated or inactivated influenza virus vaccines. J Virol. 2007 Jan;81(1):215-28. doi: 10.1128/JVI.01957-06. Epub 2006 Oct 18.

Reference Type BACKGROUND
PMID: 17050593 (View on PubMed)

Cox RJ, Brokstad KA, Zuckerman MA, Wood JM, Haaheim LR, Oxford JS. An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination. Vaccine. 1994 Aug;12(11):993-9. doi: 10.1016/0264-410x(94)90334-4.

Reference Type BACKGROUND
PMID: 7975853 (View on PubMed)

He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol. 2006 Dec;80(23):11756-66. doi: 10.1128/JVI.01460-06. Epub 2006 Sep 13.

Reference Type BACKGROUND
PMID: 16971435 (View on PubMed)

Ilyushina NA, Haynes BC, Hoen AG, Khalenkov AM, Housman ML, Brown EP, Ackerman ME, Treanor JJ, Luke CJ, Subbarao K, Wright PF. Live attenuated and inactivated influenza vaccines in children. J Infect Dis. 2015 Feb 1;211(3):352-60. doi: 10.1093/infdis/jiu458. Epub 2014 Aug 26.

Reference Type DERIVED
PMID: 25165161 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

URMC10-005/Dartmouth 22164

Identifier Type: -

Identifier Source: org_study_id