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

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT01246999
• Collaborator: National Institutes of Health (NIH) (NIH), Dartmouth-Hitchcock Medical Center (Other)
• Enrollment: 34
• Locations: 2
• Arms: 4
• Duration (Months): 32
• Patients Per Site: 17
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Live attenuated Influenza vaccine; Biological: Trivalent Influenza Vaccine; Biological: TIV followed by LAIV; Biological: LAIV followed by TIV	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Effect of Age and Prior Immunity on the Response to Live or Inactivated Seasonal (A/California/7/2009-like, A/Perth/16/2009-like, and B/Brisbane/60/2008-like (B/Victoria Lineage) Influenza Vaccines in Children
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Live Attenuated Influenza vaccine LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later	Biological: Live attenuated Influenza vaccine; 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days; Other Names: FluMist
Active Comparator: 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	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.; Other Names: Seasonal Influenza Vaccine
Active Comparator: 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	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; Other Names: Seasonal Influenza Vaccines
Active Comparator: 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	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; Other Names: Seasonal Influenza Vaccines

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR [baseline to day 7]

   Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.

Secondary Outcome Measures

1. Mean Peak H1N1 Virus Titer, Dose 1 [days 2, 4 and 7]

   After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

2. Mean Peak H3N2 Virus Titer, Dose 1 [days 2, 4 and 7]

   After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

3. Mean Peak Influenza B Virus Titer, Dose 1 [days 2, 4 and 7]

   After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

4. Mean Peak H1N1 Virus Titer, Dose 2 [days 2, 4 and 7]

   After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

5. Mean Peak H3N2 Virus Titer, Dose 2 [days 2, 4 and 7]

   After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

6. Mean Peak Influenza B Virus Titer, Dose 2 [days 2, 4 and 7]

   After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 9 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
2	Vaccine Research Unit Room 3-5000	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• National Institutes of Health (NIH)
• Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: John J. Treanor, M.D., University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Erratum in: N Engl J Med. 2007 Mar 22;356(12):1283.
• 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.
• 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. Review.
• 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.
• 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.
• 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.
• 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. Epub 2006 Sep 13.
• Maassab HF. Biologic and immunologic characteristics of cold-adapted influenza virus. J Immunol. 1969 Mar;102(3):728-32.
• 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. Epub 2006 Oct 18.
• 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. Erratum in: N Engl J Med. 2009 Jul 2;361(1):102.

• Responsible Party: John Treanor, M.D., University of Rochester
• ClinicalTrials.gov Identifier: NCT01246999
• Other Study ID Numbers: URMC10-005/Dartmouth 22164
• First Posted: Nov 24, 2010
• Last Update Posted: Dec 29, 2016
• Last Verified: Nov 1, 2016

• Keywords provided by John Treanor, M.D., University of Rochester: Influenza; A/California/7/2009-like (2009 H1N1); A/Perth/16/2009-like (H3N2); B/Brisbane/60/2008-like (B/Victoria lineage)
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	In the first year participants were randomly assigned to receive LAIV twice, TIV twice, LAIV followed by TIV or TIV followed by LAIV. In the second year, randomization was confined to 2 groups: LAIV twice or TIV followed by LAIV. 8/34 participants were in the two arms not included in the analysis.

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Period Title: Overall Study
STARTED	11	4	2	17
COMPLETED	11	3	2	15
NOT COMPLETED	0	1	0	2

Baseline Characteristics

Arm/Group Title	LAIV - LAIV	TIV - LAIV	TIV - TIV	LAIV - TIV	Total
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	TIV will be given followed by TIV 28 days later	LAIV will be given followed by TIV 28 days later	Total of all reporting groups
Overall Participants	11	4	17	2	34
Age (Count of Participants)
<=18 years	11 100%	4 100%	17 100%	2 100%	34 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Gender (Count of Participants)
Female	5 45.5%	1 25%	10 58.8%	0 0%	16 47.1%
Male	6 54.5%	3 75%	7 41.2%	2 100%	18 52.9%
Region of Enrollment (participants) [Number]
United States	11 100%	4 100%	17 100%	2 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR
Description	Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.
Time Frame	baseline to day 7

Outcome Measure Data

Analysis Population Description

Outcome for shedding of live vaccine in all participants who received a live vaccine

Arm/Group Title	Trivalent Seasonal Live Attenuated Influenza Vaccine	Seasonal Influenza Vaccine (TIV-LAIV)	All First Dose Live Vaccine
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	All subjects who received LAIV as a first dose
Measure Participants	11	15	13
shedding H1N1	1 9.1%	6 150%	9 52.9%
shedding H3N2	1 9.1%	5 125%	9 52.9%
shedding B	1 9.1%	10 250%	10 58.8%

2. Secondary Outcome

Title	Mean Peak H1N1 Virus Titer, Dose 1
Description	After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Log Mean (Standard Deviation) [log10 TCID(50)/ml]	1.8 (1.7)	0.0 (0.0)	1.4 (1.9)	0.0 (0000)

3. Secondary Outcome

Title	Mean Peak H3N2 Virus Titer, Dose 1
Description	After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Log Mean (Standard Deviation) [log10 TCID(50)/ml]	0.9 (1.6)	0 (0)	0 (0)	0 (0)

4. Secondary Outcome

Title	Mean Peak Influenza B Virus Titer, Dose 1
Description	After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Log Mean (Standard Deviation) [log10 TCID(50)/ml]	1.6 (2.0)	0 (0)	2.1 (2.9)	0 (0)

5. Secondary Outcome

Title	Mean Peak H1N1 Virus Titer, Dose 2
Description	After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Mean (Standard Deviation) [log10 TCID(50)/ml]	0.3 (0.99)	0 (0)	0 (0)	1 (1.8)

6. Secondary Outcome

Title	Mean Peak H3N2 Virus Titer, Dose 2
Description	After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Mean (Standard Deviation) [log10 TCID(50)/ml]	0.3 (0.9)	0 (0)	0 (0)	0.3 (1.2)

7. Secondary Outcome

Title	Mean Peak Influenza B Virus Titer, Dose 2
Description	After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Time Frame	days 2, 4 and 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV - LAIV	TIV - LAIV	LAIV - TIV	TIV - TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days	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 Seasonal Influenza Vaccine TIV/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	LAIV will be given intranasally followed by TIV intramuscularly	TIV will be given IM followed by TIV IM
Measure Participants	11	3	2	15
Mean (Standard Deviation) [log10 TCID(50)/ml]	0 (0)	0 (0)	0 (0)	1.3 (2)

Adverse Events

Arm/Group Title	LAIV-LAIV		TIV-LAIV		LAIV-TIV		TIV-TIV
Arm/Group Description	LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days		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 Seasonal Influenza Vaccine TIV/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		LAIV will be given intranasally followed by TIV intramuscularly		TIV will be given IM followed by IV IM
All Cause Mortality
	LAIV-LAIV		TIV-LAIV		LAIV-TIV		TIV-TIV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LAIV-LAIV		TIV-LAIV		LAIV-TIV		TIV-TIV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/15 (0%)		0/2 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	LAIV-LAIV		TIV-LAIV		LAIV-TIV		TIV-TIV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)		3/15 (20%)		1/2 (50%)		12/17 (70.6%)
Ear and labyrinth disorders
ear ache	0/11 (0%)		1/15 (6.7%)		0/2 (0%)		0/17 (0%)
Eye disorders
eye redness	1/11 (9.1%)		1/15 (6.7%)		0/2 (0%)		0/17 (0%)
General disorders
fever	0/11 (0%)		1/15 (6.7%)		0/2 (0%)		2/17 (11.8%)
fatigue	3/11 (27.3%)		0/15 (0%)		1/2 (50%)		0/17 (0%)
body ache	0/11 (0%)		0/15 (0%)		0/2 (0%)		2/17 (11.8%)
nose bleed	0/11 (0%)		1/15 (6.7%)		0/2 (0%)		1/17 (5.9%)
Infections and infestations
sore throat	1/11 (9.1%)		1/15 (6.7%)		0/2 (0%)		1/17 (5.9%)
stuffy nose	6/11 (54.5%)		2/15 (13.3%)		1/2 (50%)		4/17 (23.5%)
Nervous system disorders
headache	0/11 (0%)		0/15 (0%)		0/2 (0%)		1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
runny nose	3/11 (27.3%)		2/15 (13.3%)		0/2 (0%)		3/17 (17.6%)
cough	5/11 (45.5%)		2/15 (13.3%)		0/2 (0%)		5/17 (29.4%)
wheezing	0/11 (0%)		0/15 (0%)		0/2 (0%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
pain at the injection site	0/11 (0%)		2/15 (13.3%)		0/2 (0%)		8/17 (47.1%)
tenderness at the injection site	0/11 (0%)		3/15 (20%)		0/2 (0%)		8/17 (47.1%)
swelling at the injection site	0/11 (0%)		0/15 (0%)		0/2 (0%)		1/17 (5.9%)
redness at the injection site	0/11 (0%)		0/15 (0%)		0/2 (0%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.