Influenza
Conditions
Keywords
Trivalent, inactivated influenza vaccine, High-Dose trivalent, inactivated influenza vaccine, Adult and elderly identical twins, Adult fraternal twins
Brief summary
This study will investigate markers, mechanisms and define general predictors for immunological health by comparing influenza vaccine responses in monozygotic and dizygotic twins.
Detailed description
The investigators plan to study the response to influenza vaccines much more broadly and deeply across different age groups and with different vaccine formulations and to probe the influence of genetics on these responses using monozygotic and dizygotic twins. On an investigational basis, investigators plan to compare various immunological responses, identify age-specific biomarkers or clusters of markers, quantify the frequency of influenza-specific T-cells pre- and post-vaccination, and determine the effective breadth of T-cell repertoire to an influenza vaccine within an individual as a function of age and to what degree this is genetically determined. Twin Groups B-E will receive a single administration of the 2011-2012 formulation of seasonal trivalent inactivated influenza vaccine (TIV). Group F, elderly monozygotic twin participants, will be randomly assigned to receive a single dose of inactivated vaccine, either the usual dose or the High-Dose TIV. Blood samples to conduct the assays described will be taken at pre-immunization, Days 7-10 and 28 post-immunization. The number of individual participants, not the number of twin pairs is being reported in all the modules.
Interventions
BIOLOGICALTIV
Influenza Virus Vaccine Suspension for Intramuscular Injection
BIOLOGICALHigh-Dose TIV
High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe for intramuscular injection
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
1. Otherwise healthy, ambulatory adults, ages 18-30 years (identical or fraternal twin pairs), 40-64 years (identical or fraternal twin pairs) or 65-100 years (identical twin pairs). 2. Willing to complete the informed consent process. 3. Availability for follow-up for the planned duration of the study at least 28 days after immunization. 4. Acceptable medical history and vital signs.
Exclusion criteria
1. Prior off-study vaccination with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV) in Fall 2011 2. Allergy to egg or egg products, or to vaccine components, including thimerosal (if TIV multidose vials used) 3. Allergy to latex (for Group F only - may be assigned to Fluzone High-Dose). Review with investigator. 4. Life-threatening reactions to previous influenza vaccinations 5. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination 6. History of immunodeficiency (including HIV infection) 7. 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. 8. Blood pressure \>150 systolic or \> 95 diastolic at Visit 1 9. Hospitalization in the past year for congestive heart failure or emphysema. 10. Chronic Hepatitis B or C 11. Recent or current use of immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays, topical steroids and inhaled steroids are permissible). Use of oral steroids (\<20mg prednisone-equivalent/day) may be acceptable after review by the investigator. 12. 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). 13. 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. 14. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year 15. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except aspirin up to 325 mg.day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety. 16. Receipt of blood or blood products within the past 6 months 17. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol 18. Inactivated vaccine 14 days prior to vaccination 19. Live, attenuated vaccine within 60 days of vaccination 20. History of Guillain-Barre Syndrome 21. Pregnant or lactating woman 22. Use of investigational agents within 30 days prior to enrollment 23. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment 24. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Individual Twins Who Received Influenza Vaccine | Day 0 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Individual Twins With Related Adverse Events | Day 0 to 28 post-immunization |
Participant flow
Recruitment details
Numbers listed in the tables reflect individual twins and not twin pairs.
Participants by arm
| Arm | Count |
|---|---|
| Group B: 18-30 yo Identical Twins (TIV) Individual twins to receive Fluzone® standard TIV
Fluzone® standard TIV: Influenza Virus Vaccine Suspension for Intramuscular Injection | 8 |
| Group C: 18-30 yo Fraternal Twins (TIV) Individual twins to receive Fluzone® standard TIV
Fluzone® standard TIV: Influenza Virus Vaccine Suspension for Intramuscular Injection | 10 |
| Group D: 40-64 yo Identical Twins (TIV) Individual twins to receive Fluzone® standard TIV
Fluzone® standard TIV: Influenza Virus Vaccine Suspension for Intramuscular Injection | 23 |
| Group E: 40-64 yo Fraternal Twins (TIV) Individual twins to receive Fluzone® standard TIV
Fluzone® standard TIV: Influenza Virus Vaccine Suspension for Intramuscular Injection | 12 |
| Group F: 65-100 yo Identical Twins (TIV) Individual twins will receive Fluzone® standard TIV: Influenza Virus Vaccine Suspension for Intramuscular Injection | 5 |
| Group F: 65-100 yo Identical Twins (High-DoseTIV) Individual twins will receive Fluzone® high-dose TIV: High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe for Intramuscular Injection | 5 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | 3 subjects consented but not vaccinated | 0 | 0 | 3 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group B: 18-30 yo Identical Twins (TIV) | Total | Group F: 65-100 yo Identical Twins (High-DoseTIV) | Group F: 65-100 yo Identical Twins (TIV) | Group E: 40-64 yo Fraternal Twins (TIV) | Group D: 40-64 yo Identical Twins (TIV) | Group C: 18-30 yo Fraternal Twins (TIV) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 24.79 years STANDARD_DEVIATION 4.18 | 47.55 years STANDARD_DEVIATION 16.46 | 70.08 years STANDARD_DEVIATION 3.83 | 70.08 years STANDARD_DEVIATION 3.83 | 55.86 years STANDARD_DEVIATION 7.1 | 50.55 years STANDARD_DEVIATION 7.03 | 26.37 years STANDARD_DEVIATION 3.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 9 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 53 Participants | 5 Participants | 5 Participants | 10 Participants | 20 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 53 Participants | 5 Participants | 5 Participants | 9 Participants | 20 Participants | 8 Participants |
| Region of Enrollment United States | 8 participants | 63 participants | 5 participants | 5 participants | 12 participants | 23 participants | 10 participants |
| Sex: Female, Male Female | 6 Participants | 42 Participants | 3 Participants | 3 Participants | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 21 Participants | 2 Participants | 2 Participants | 5 Participants | 8 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 | 0 / 20 | 0 / 12 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 8 | 1 / 10 | 1 / 20 | 0 / 12 | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 | 0 / 20 | 0 / 12 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Number of Individual Twins Who Received Influenza Vaccine
Time frame: Day 0
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group B: 18-30 yo Identical Twins (TIV) | Number of Individual Twins Who Received Influenza Vaccine | 8 Participants |
| Group C: 18-30 yo Fraternal Twins (TIV) | Number of Individual Twins Who Received Influenza Vaccine | 10 Participants |
| Group D: 40-64 yo Identical Twins (TIV) | Number of Individual Twins Who Received Influenza Vaccine | 20 Participants |
| Group E: 40-64 yo Fraternal Twins (TIV) | Number of Individual Twins Who Received Influenza Vaccine | 12 Participants |
| Group F: 65-100 yo Identical Twins (TIV) | Number of Individual Twins Who Received Influenza Vaccine | 5 Participants |
| Group F: 65-100 yo Identical Twins (High-DoseTIV) | Number of Individual Twins Who Received Influenza Vaccine | 5 Participants |
Secondary
Number of Individual Twins With Related Adverse Events
Time frame: Day 0 to 28 post-immunization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group B: 18-30 yo Identical Twins (TIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |
| Group C: 18-30 yo Fraternal Twins (TIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |
| Group D: 40-64 yo Identical Twins (TIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |
| Group E: 40-64 yo Fraternal Twins (TIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |
| Group F: 65-100 yo Identical Twins (TIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |
| Group F: 65-100 yo Identical Twins (High-DoseTIV) | Number of Individual Twins With Related Adverse Events | 0 Participants |