Evaluation of the Effects of Age, Prior Exposure, and Previous Vaccination on Response to the Flu Vaccine

Influenza, Human Clinical Trial

Official title:

Evaluation of the Effects of Age, Prior Exposure, and Previous Vaccination on the B Cell Response to Inactivated Influenza Vaccine in Healthy Adults and Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03133936
• Other study ID #: RSRB00065443
• Status: Completed
• Phase: N/A
• Start date: December 2016
• Est. completion date: June 2020

Study information

• Verified date: July 2020
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the immune response in recipients of the vaccine. After participants receive the vaccine, samples of blood will be obtained at several intervals afterwards. These blood samples will be used to measure the immune response to the vaccine. Everyone in this study will receive a single dose of flu vaccine, and have blood samples drawn to measure the immune response over the next 90 days. The investigators will also ask participants to report any flu like illnesses during the flu season, and if participants develop a fever or cough, to come in to be tested for flu. This will allow the investigators to compare the vaccine response between people who got the flu and those who did not.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: June 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Years and older

Eligibility

Inclusion Criteria:

1. Aged equal to or greater than 9 years of age.

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

3. The subject must be in good health, as determined by: vital signs (heart rate >45 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.

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

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

6. 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.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

Biological:
• Fluarix
Fluarix (GSK). Quadrivalent (IIV-4) subvirion vaccine produced in embryonated hen's eggs and administered intramuscularly at a dose of not less than 15 ug of HA (as determined by SRID) per component.

Locations

Country	Name	City	State
United States	University of Rochester Medical Center, Vaccine Research Unit Room 3-5000	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean frequency of Peripheral blood antibody secreting cells	B cell ELISPOT assays will be performed on plates coated with recombinant HA proteins that match the influenza strains in that years vaccine	day 7
Primary	Mean antibody titer of peripheral blood antibody secreting cells	Cultured plasmablasts will be analyzed by hemagglutination inhibition assay	day 7
Primary	Change in mean frequency of Peripheral blood memory B cells	B cell ELISPOT assays will be performed on plates coated with recombinant HA proteins that match the influenza strains in that years vaccine	baseline to day 90
Primary	Change in mean antibody titer of peripheral blood memory B cells	Cultured plasmablasts will be analyzed by hemagglutination inhibition assay	baseline to day 90
Primary	Change in mean antibody titer	Sera will be tested by microtiter technique for neutralization of the vaccine viruses in MDCK cells. Viral growth will be determined by ELISA of the cells following fixation with methanol using a combination of M- and NP-specific monoclonal antibodies. The titer of antibody will be defined as the highest titer resulting in 50% inhibition of antigen signal compared to un-neutralized control wells. Sera will be treated with RDE and heat inactivated prior to testing at an initial starting dilution of 1:10. Sera with no neutralizing titer will be assigned a value of 1:5 for calculation purposes.	baseline to day 90
Primary	Change in the mean off rate of antibody antigen binding	Sera will be evaluated for avidity by SPR, SPR measures the off rate (rate at which antibodies dissociate from the antigen) of antibody-antigen binding. The off rates provide a measure of how well the antibodies bind, indicating their quality. In an ideal immune response to vaccine, the off rates should go down, indicating an improved recognition of antigen. For these studies, the SPR array of antigens will be the recombinant influenza hemagglutinins that match that year's vaccine formulation, as well as HA head only and HA stalk only recombinant proteins.	baseline to day 90
Primary	The change in the number of reactive antigen epitopes	The specificity of HA binding antibodies will be determined by reactivity with a library of random epitopes created by genome fragment phage display. The phage display libraries are created using molecular methods that break the hemagglutinin gene into random segments that code for HA peptides between 50 and 350 amino acids in length.	baseline to day 90
Secondary	Change in mean antibody titer of peripheral blood memory B cells	Cultured plasmablasts will be analyzed by hemagglutination inhibition assay	day 90
Secondary	Change in mean antibody titer	Sera will be tested by microtiter technique for neutralization of the vaccine viruses in MDCK cells. Viral growth will be determined by ELISA of the cells following fixation with methanol using a combination of M- and NP-specific monoclonal antibodies. The titer of antibody will be defined as the highest titer resulting in 50% inhibition of antigen signal compared to un-neutralized control wells. Sera will be treated with RDE and heat inactivated prior to testing at an initial starting dilution of 1:10. Sera with no neutralizing titer will be assigned a value of 1:5 for calculation purposes.	day 90
Secondary	Change in the mean off rate of antibody antigen binding	Sera will be evaluated for avidity by SPR, SPR measures the off rate (rate at which antibodies dissociate from the antigen) of antibody-antigen binding. The off rates provide a measure of how well the antibodies bind, indicating their quality. In an ideal immune response to vaccine, the off rates should go down, indicating an improved recognition of antigen. For these studies, the SPR array of antigens will be the recombinant influenza hemagglutinins that match that year's vaccine formulation, as well as HA head only and HA stalk only recombinant proteins.	day 90
Secondary	The change in the number of reactive antigen epitopes	The specificity of HA binding antibodies will be determined by reactivity with a library of random epitopes created by genome fragment phage display. The phage display libraries are created using molecular methods that break the hemagglutinin gene into random segments that code for HA peptides between 50 and 350 amino acids in length.	day 90