Comparison of Three Licensed Influenza Vaccines

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT03068949
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 413
• Location: 1
• Arms: 4
• Actual Duration (Months): 68.1
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

This study will evaluate in detail the way that the immune system responds to three different kinds of flu shots that are licensed in the United States.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: FluBlok; Biological: Fluzone; Biological: FluCelVax; Biological: Fluzone HD	Phase 4

Detailed Description

Previous observations to date lead to the following model: Traditional egg-derived TIV have contaminating internal virion proteins that preferentially elicit memory CD4 T cells specific for these proteins. These CD4 T cells will have limited efficacy as helpers for the neutralizing Ab response and will suppress the CD4 T cell response to new HA epitopes in the vaccine. The current study will test this hypothesis by comparing CD4 cell responses to specific epitopes, and the subsequent B cell and antibody response, in subjects receiving a vaccine containing only HA protein to vaccines with more complex antigenic characteristics. The CD4 T cell reactivity to pools of unique, conserved, and total pH1 HA peptides as well as H3, influenza B HA, NP, and M1 peptides will be quantified using cytokine Elispot assays and flow cytometry, and then compared to the subsequent antibody and B cell response.

Investigators will also use this study as an opportunity to evaluate the effects of prior vaccination. Recent studies have emphasized the potential negative effect of vaccination in prior years on both the immune response as well as the protective effectiveness of current vaccine. In order to evaluate this phenomenon in the context of multiple vaccine formulations, prior vaccination history of the subjects will be reviewed and subjects stratify vaccination based on vaccine history.

In addition, subjects who participated in this study in a previous year are eligible to re-enroll, and will receive the same vaccine that they were randomized to previously. This will allow an evaluation of differences between vaccine formulations in the responsiveness to multiple vaccinations.

Furthermore, recent studies indicate reports that the glycosylation pattern of viral hemagglutinins produced in cell culture can vary depending on the host cell used, and that this can affect CD4 T cell immunogenicity and antibody recognition. As a cell culture-based influenza vaccine production platform offers many advantages and may eventually supplant the traditional egg-based approach, it is of great value to understand the CD4 T cell response induced by this vaccine and how this affects neutralizing Ab production.

Recent data have also suggested that the failure of seasonal influenza infection to induce substantial levels of stalk specific antibody may be due to the relatively inaccessible nature of this epitope. As part of this study, investigators will also compare the specificity of the human antibody response between the vaccine groups, with the hypothesis that the rHA vaccine will more readily allow targeting of these important, broadly conserved epitopes. There is compelling preliminary data demonstrating that multiple antibodies that we have isolated have a particularly slow on rate when they bind to the HA-stalk versus the HA-globular head epitopes on whole virions, but not on recombinant HA trimmers expressed in baculovirus. The hypothesis is that a free, recombinant HA vaccine will allow more efficient targeting of the HA-Stalk epitopes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 413 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Comparison of CD4 T Cell Induction and Antibody Responses Between a Pure Hemagglutinin Influenza Vaccine and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Healthy Adults.
• Actual Study Start Date: Oct 28, 2015
• Actual Primary Completion Date: Jun 30, 2020
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FluBlok FluBlok 0.5 mL given IM X1	Biological: FluBlok; FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly
Active Comparator: Fluzone Fluzone 0.5 mL given IM X1	Biological: Fluzone; Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly
Active Comparator: FluCelVax FluCelVax 0.5 mL given IM X 1	Biological: FluCelVax; FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly
Active Comparator: Fluzone HD Fluzone HD 0.5 mL given IM X1	Biological: Fluzone HD; Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly

Outcome Measures

Primary Outcome Measures

1. Mean Change of HAI Serum Antibody Titers to A/California/07/09 (H1N1) [Day 0 to Day 28]

   Mean change of HAI serum antibody titers to A/California/07/09 (H1N1) using serum hemagglutination-inhibition (HAI) assay.

2. Mean Change of HAI Serum Antibody Titers to A/Michigan/45/2015 (H1N1) [Day 0 to Day 28]

   Mean Change of HAI Serum Antibody Titers to A/Michigan/45/2015 (H1N1) using serum hemagglutination-inhibition (HAI) assay.

3. Mean Change of HAI Serum Antibody Titers to A/Switzerland/9715293/13 (H3N2) [Day 0 to Day 28]

   Mean Change of HAI Serum Antibody Titers to A/Switzerland/9715293/13 (H3N2)

4. Mean Change of MN Serum Antibody Titers to A/California/07/09 (H1N1) [Day 0 to Day 28]

   Mean Change of MN Serum Antibody Titers to A/California/07/09 (H1N1) using Microneutralization (MN) assay.

5. Mean Change of MN Serum Antibody Titers to A/Michigan/45/2015 (H1N1) [Day 0 to Day 28]

   Mean Change of MN Serum Antibody Titers to A/Michigan/45/2015 (H1N1) using Microneutralization (MN) assay.

6. Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From pH1N1 HA [Day 0 to Day 14]

   Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from pH1N1 HA using cytokine Elispot

7. Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From H3 HA [Day 0 to Day 14]

   Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from H3 HA using cytokine Elispot

8. Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From Influenza B HA [Day 0 to Day 14]

   Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from influenza B HA using cytokine Elispot.

9. Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From NP [Day 0 to Day 14]

   Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from NP using cytokine Elispot.

10. Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From M1 [Day 0 to Day 14]

    Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from M1 using cytokine Elispot.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Aged between 18 and 49 years of age (inclusive).

2. Female subjects must fulfill one of the following: (i) not able to bear children because she has been surgically sterilized (tubal ligation or hysterectomy) or (ii) agrees to practice effective methods of contraception that may include, but are not limited to abstinence, barrier methods, monogamous relationship with vasectomized partner, birth control pills, patches, hormonal shots or hormonal implants, NuvaRing and IUDs (intrauterine devices), from 30 days prior to study enrollment through 30 days following receipt of the last dose of vaccine.

3. Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) within 24 hours prior to vaccination.

4. The subject must be in good health, as determined by: vital signs (heart rate >55 to <100 bpm; blood pressure: systolic ≥ 90 mm Hg and ≤150 mm Hg; diastolic ≤ 90 mm Hg; oral temperature <100.0ºF); 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.

5. The subject is able to understand and comply with the planned study procedures, including being available for all study visits.

6. The subject has provided informed consent prior to any study procedures.

7. Subjects who have not received seasonal flu vaccine for the current year.

Exclusion Criteria

1. Subject report of known hypersensitivity to allergy to components of the study vaccine or other components of the study vaccine.

2. Subject report of known latex allergy

3. Subject report of a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.

4. Subject report of a history of Guillain-Barre syndrome within 6 weeks of receipt of a previous influenza vaccine.

5. The subject is a woman who is pregnant or breastfeeding or intends to become pregnant during the study period between enrollment and 30 days following receipt of vaccine.

6. 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 within the preceding 36 months.

7. The subject has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy. For this criterion, "active" is defined as having received treatment within the past 5 years.

8. The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).

9. The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study.

10. 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.

11. The subject has an acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include any acute or chronic medical disease or conditions defined as persisting for 3 months (defines ad 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses of the subject's successful completion of the study.

12. Subjects with an active infection or that has an acute illness or an oral temperature greater than 99.9F (37.7C) 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 resolved > 3 days prior to enrollment.

13. 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.

14. 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.

15. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years.

16. The subject has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis, or is receiving psychiatric drugs. Subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensation are allowed enrollment into the study.

17. The subject has a history of alcohol or drug abuse in the 5 years prior to enrollment.

18. The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection.

19. 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	University of Rochester Medical Center, Vaccine Research Unit Room 3-5000	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Angela Branche, MD, University of Rochester

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 8, 2021

More Information

Publications

None provided.

• Responsible Party: Angela Branche, Assistant Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT03068949
• Other Study ID Numbers: 59331; 272201400005C-P00019-9999-4
• First Posted: Mar 3, 2017
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Period Title: Overall Study
STARTED	113	102	122	76
COMPLETED	105	90	113	63
NOT COMPLETED	8	12	9	13

Baseline Characteristics

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD	Total
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly	Total of all reporting groups
Overall Participants	113	102	122	76	413
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.2 (16.7)	29.0 (10.2)	33.4 (15.6)	35.9 (18.0)	33.0 (15.3)
Sex: Female, Male (Count of Participants)
Female	72 63.7%	52 51%	67 54.9%	39 51.3%	230 55.7%
Male	41 36.3%	50 49%	55 45.1%	37 48.7%	183 44.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 0.9%	5 4.9%	11 9%	5 6.6%	22 5.3%
Not Hispanic or Latino	112 99.1%	97 95.1%	111 91%	71 93.4%	391 94.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Change of HAI Serum Antibody Titers to A/California/07/09 (H1N1)
Description	Mean change of HAI serum antibody titers to A/California/07/09 (H1N1) using serum hemagglutination-inhibition (HAI) assay.
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

HAI serum antibody titers to A/California/07/09 (H1N1) for Fluzone HD arm are unavailable. Fluzone HD group was only enrolled in flu seasons Fall 2017 - Fall 2019. HAI serum antibody titers to A/California/07/09 (H1N1) was only tested on subjects enrolled in Fall 2015 and Fall 2016.

Arm/Group Title	FluBlok	Fluzone	FluCelVax
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly
Measure Participants	32	31	38
Geometric Mean (95% Confidence Interval) [titer]	1937	383	607

2. Primary Outcome

Title	Mean Change of HAI Serum Antibody Titers to A/Michigan/45/2015 (H1N1)
Description	Mean Change of HAI Serum Antibody Titers to A/Michigan/45/2015 (H1N1) using serum hemagglutination-inhibition (HAI) assay.
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	23	25	30	22
Geometric Mean (95% Confidence Interval) [titer]	564	420	354	898

3. Primary Outcome

Title	Mean Change of HAI Serum Antibody Titers to A/Switzerland/9715293/13 (H3N2)
Description	Mean Change of HAI Serum Antibody Titers to A/Switzerland/9715293/13 (H3N2)
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

HAI serum antibody titers to A/Switzerland/9715293/13 (H3N2) for Fluzone HD arm are unavailable. Fluzone HD group was only enrolled in flu seasons Fall 2017 - Fall 2019. HAI serum antibody titers to A/Switzerland/9715293/13 (H3N2) was only tested on subjects enrolled in Fall 2015 and Fall 2016.

Arm/Group Title	FluBlok	Fluzone	FluCelVax
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly
Measure Participants	32	31	38
Geometric Mean (95% Confidence Interval) [titer]	1733	1711	799

4. Primary Outcome

Title	Mean Change of MN Serum Antibody Titers to A/California/07/09 (H1N1)
Description	Mean Change of MN Serum Antibody Titers to A/California/07/09 (H1N1) using Microneutralization (MN) assay.
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

MN serum antibody titers to A/California/07/09 (H1N1) for Fluzone HD arm are unavailable. Fluzone HD group was only enrolled in flu seasons Fall 2017 - Fall 2019. MN serum antibody titers to A/California/07/09 (H1N1) was only tested on subjects enrolled in Fall 2015 and Fall 2016.

Arm/Group Title	FluBlok	Fluzone	FluCelVax
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly
Measure Participants	32	31	38
Geometric Mean (95% Confidence Interval) [titer]	2786	373	881

5. Primary Outcome

Title	Mean Change of MN Serum Antibody Titers to A/Michigan/45/2015 (H1N1)
Description	Mean Change of MN Serum Antibody Titers to A/Michigan/45/2015 (H1N1) using Microneutralization (MN) assay.
Time Frame	Day 0 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	23	25	30	22
Geometric Mean (95% Confidence Interval) [titer]	1007	554	308	1477

6. Primary Outcome

Title	Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From pH1N1 HA
Description	Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from pH1N1 HA using cytokine Elispot
Time Frame	Day 0 to Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	50	49	51	21
Mean (Standard Error) [cells per million CD8- and CD56- PBMC]	71.2 (97.4)	21.4 (57.3)	29.5 (92.8)	39.8 (84.7)

7. Primary Outcome

Title	Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From H3 HA
Description	Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from H3 HA using cytokine Elispot
Time Frame	Day 0 to Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	50	49	51	21
Mean (Standard Error) [cells per million CD8- and CD56- PBMC]	93.2 (128.0)	14.0 (69.8)	21.5 (157.3)	58.6 (162.7)

8. Primary Outcome

Title	Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From Influenza B HA
Description	Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from influenza B HA using cytokine Elispot.
Time Frame	Day 0 to Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	50	49	51	21
Mean (Standard Error) [cells per million CD8- and CD56- PBMC]	178.0 (218.8)	89.2 (162.1)	79.0 (203.5)	42.1 (171.6)

9. Primary Outcome

Title	Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From NP
Description	Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from NP using cytokine Elispot.
Time Frame	Day 0 to Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	49	49	51	20
Mean (Standard Error) [cells per million CD8- and CD56- PBMC]	-23.9 (81.3)	-9.7 (95.5)	-16.9 (128.1)	19.6 (165.2)

10. Primary Outcome

Title	Mean Change in CD4 T Cells Reactivity to Pools of Total pHA Peptides Derived From M1
Description	Mean change in CD4 T cells reactivity to pools of total pHA peptides derived from M1 using cytokine Elispot.
Time Frame	Day 0 to Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FluBlok	Fluzone	FluCelVax	Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly	Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly	FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly	Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Measure Participants	50	49	51	21
Mean (Standard Error) [cells per million CD8- and CD56- PBMC]	-18.9 (99.7)	-18.7 (118.0)	20.9 (143.8)	-36.3 (212.3)

Adverse Events

Time Frame	6 months
Arm/Group Title	FluBlok		Fluzone		FluCelVax		Fluzone HD
Arm/Group Description	FluBlok 0.5 mL given IM X1 FluBlok: FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly		Fluzone 0.5 mL given IM X1 Fluzone: Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly		FluCelVax 0.5 mL given IM X 1 FluCelVax: FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly		Fluzone HD 0.5 mL given IM X1 Fluzone HD: Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
All Cause Mortality
	FluBlok		Fluzone		FluCelVax		Fluzone HD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/113 (0%)		0/102 (0%)		0/122 (0%)		0/76 (0%)
Serious Adverse Events
	FluBlok		Fluzone		FluCelVax		Fluzone HD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/113 (0%)		0/102 (0%)		0/122 (0%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	FluBlok		Fluzone		FluCelVax		Fluzone HD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/113 (31.9%)		30/102 (29.4%)		45/122 (36.9%)		28/76 (36.8%)
Cardiac disorders
chest pain	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
heart palpitations	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
pericarditis	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
tachycardia	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
Ear and labyrinth disorders
middle ear effusion	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	2
right ear pain	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
Endocrine disorders
thyroid nodules	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
Eye disorders
bilateral conjunctivities	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
dry eye	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
eyelid swelling	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
Gastrointestinal disorders
abdomina l pain	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
diarrhea	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
gastrointestional illness	0/113 (0%)	0	0/102 (0%)	0	2/122 (1.6%)	2	0/76 (0%)	0
nausea	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
nausea and vomiting	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
vomiting	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
stomach ache	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
General disorders
chills	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
chipped tooth/dentral extraction	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
sore throat	1/113 (0.9%)	1	3/102 (2.9%)	3	4/122 (3.3%)	4	3/76 (3.9%)	3
tooth ache	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
feverish	2/113 (1.8%)	2	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
fatigue	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	2/76 (2.6%)	2
headache	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	3/76 (3.9%)	3
myalgia	1/113 (0.9%)	1	0/102 (0%)	0	1/122 (0.8%)	1	1/76 (1.3%)	1
dizziness	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
fatigue	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
lethargy	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
lightheadedness	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
malaise	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
sneezing	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
rhinitis	1/113 (0.9%)	1	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
vaginal spotting	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
right labral pain	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
Infections and infestations
sinusitis	0/113 (0%)	0	1/102 (1%)	1	3/122 (2.5%)	3	1/76 (1.3%)	1
strep throat	0/113 (0%)	0	1/102 (1%)	3	0/122 (0%)	0	0/76 (0%)	0
urinary tract infection	2/113 (1.8%)	4	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
yeast infection	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
tooth infection	1/113 (0.9%)	1	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
otitis media	1/113 (0.9%)	1	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
serous otitis	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
influenza like illness	0/113 (0%)	0	2/102 (2%)	2	0/122 (0%)	0	1/76 (1.3%)	1
influenza	2/113 (1.8%)	2	0/102 (0%)	0	2/122 (1.6%)	2	0/76 (0%)	0
Musculoskeletal and connective tissue disorders
back pain	2/113 (1.8%)	2	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
body aches	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
foot pain due to bone chip	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
fractured right thumb	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
knee replacement surgery	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
left wrist pain secondary to electric shock	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
left arm pain	0/113 (0%)	0	0/102 (0%)	0	0/122 (0%)	0	1/76 (1.3%)	1
left arm laceration	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
right ankle sprain	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
right elbow pain	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
sensation of heaviness and heat of legs	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
tendon sheath inflammation	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
rigth breast lump	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
Nervous system disorders
concussion	0/113 (0%)	0	2/102 (2%)	2	0/122 (0%)	0	0/76 (0%)	0
trembling in hands	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
migraine headache	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
tingling in both hands	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
Respiratory, thoracic and mediastinal disorders
bronchitis	1/113 (0.9%)	1	1/102 (1%)	1	1/122 (0.8%)	1	0/76 (0%)	0
congestion	3/113 (2.7%)	3	2/102 (2%)	2	4/122 (3.3%)	4	0/76 (0%)	0
Uri	18/113 (15.9%)	21	21/102 (20.6%)	21	24/122 (19.7%)	26	14/76 (18.4%)	17
Skin and subcutaneous tissue disorders
alopecia	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
injection site bruise	1/113 (0.9%)	1	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
injection site erythema	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
injection site hematoma	0/113 (0%)	0	0/102 (0%)	0	1/122 (0.8%)	1	0/76 (0%)	0
injection site pain	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	1/76 (1.3%)	1
injection site swelling	0/113 (0%)	0	1/102 (1%)	1	0/122 (0%)	0	0/76 (0%)	0
contact dermatitis	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0
psoriasis	1/113 (0.9%)	1	0/102 (0%)	0	0/122 (0%)	0	0/76 (0%)	0

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.