Influenza
Conditions
Keywords
Innate immunity, Adaptive immunity, Slu shot, Elderly
Brief summary
Vaccination is the most effective way of preventing infectious diseases. Despite the success of vaccines in general, vaccines induce diminished antibody responses and lower protection in the elderly in particular. This could be explained by a defect in the early responses of an ageing immune system. A better understanding of the basic immunological mechanisms that mediate vaccine efficacy is incomplete. Such information is critical and could greatly decrease both the cost and the time to new vaccine development particularly for the geriatric population. In this trial, the investigators will study the immunologic differences of an FDA approved licensed influenza vaccine between a younger and an older group. Twenty two healthy volunteers between the age of 25-40 and forty four healthy volunteers above the age of 65 will be enrolled in the study. Each participant in the study will be given one flu shot. Blood work will be obtained prior to vaccination, one day, three days, seven days, fourteen days, as well as one month and six months after vaccination. Throughout the duration of the study, the participants will be monitored for safety.
Detailed description
RATIONALE:Trivalent Influenza vaccine (TIV) is known to induce diminished functional antibody responses and lower protection in the elderly. Here we hypothesize that this is due to intrinsic defects in innate responses which translates into suboptimal Hemagglutination Inhibition Assay (HAI) titers. Therefore, early innate signatures of vaccination should correlate with, and predict the immunogenicity of TIV in the young and elderly. STUDY DESIGN: Single center, open label study in which adult healthy volunteers with no contraindications to immunization will be vaccinated with TIV. Blood samples will be collected on Days D0 (at enrollment) and D1, D3, D7, D14, D30, D180 post vaccination to study innate and/or adaptive immunity markers. Even though influenza vaccination is considered safe, volunteers will be asked to report any local or systemic adverse events (AEs) from Day 0 (vaccination) to Day 7 in memory aids. Reactogenicity events will also be evaluated by injection site examination on visits at D0, D1, D3 and D7. Volunteers will be also asked to report local and systemic AEs developing the day of a blood draw. Additionally, only AEs considered related (unlikely, possibly, probably or definitely related) will be collected and reported in this study from Day 0 (vaccination) to Day 180. After Day 30 only related SAEs will be collected and reported.
Interventions
BIOLOGICALtrivalent Influenza vaccine (TIV)
0.5 ml IM as a single dose in a prefilled syringe.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Healthy individuals aged 25-40 years, or ≥65 years old. 2. Able to understand and give informed consent. 3. Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are not postmenopausal for ≥1 year) must agree to practice adequate contraception that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms, diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for 30 days before and 30 days after trivalent Influenza vaccination.
Exclusion criteria
1. Receipt of immune products: * Receipt of blood products 3 months prior to study entry or expected receipt through 6 months after study entry * Receipt of any live virus vaccines within 4 weeks prior to study entry or expected receipt within 4 weeks after study entry\* * Receipt of any inactivated vaccine within 2 weeks or expected receipt within 2 weeks after study entry\* * Receipt of the 2010-2011 influenza vaccine 2. Documented influenza infection during the 2010-2011 influenza season. Not excluded from the study, volunteers with prior upper respiratory infections during the 2010-2011 influenza illness. 3. Presence of co-morbidities or immunosuppressive states such as: * Chronic medical problems including (but not limited to) insulin dependent diabetes, severe heart disease, severe lung disease, severe liver disease, severe kidney disease, auto immune diseases, severe gastrointestinal diseases, and uncontrolled hypertension. * Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data. * Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C; organ transplant; cancer; current and/or expected receipt of chemotherapy, radiation therapy or any other cytotoxic or immunosuppressive therapy \[i.e. more than 10 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 3 months\*; receipt of high-dose inhaled steroids is also an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy, Measured by the Number of Subjects With a Change in Innate Immune Signatures | Day 0 (prior to TIV administration), Day 180 (from the time of of TIV administration) | The number of subjects with a change in innate immunity signatures correlating with the level of antibodies was recorded. The innate immune signatures were assessed by Fluorescence Activated Cell Sorting (FACS)/Luminex assays. The levels of antibodies to the influenza virus prior to TIV (trivalent influenza vaccine) administration and on Day 180 after receiving TIV was assessed and the number of subjects who exhibited an increase in the antibodies and, therefore, a change in their innate immune signatures, was recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Specific B Cell Responses That Correlate With the Innate Immune Signatures | 2 years | The secondary outcomes will identify the number of participants with a positive B cell response to the flu shot particulary looking for antibody responses, presence of plasmablasts, antibody repertoire. |
Countries
United States
Participant flow
Recruitment details
Atlanta Metropolitan Area 2010-2011
Pre-assignment details
There were 4 screen failures : * one unable to obtain blood pre-vaccination * two with elevated blood pressure readings * one with progressive medical illness
Participants by arm
| Arm | Count |
|---|---|
| Age 25-40 Years Healthy participants between the ages of 25 to 40 years of age received 0.5 ml of the trivalent Influenza vaccine (TIV) administered via the intramuscular route in the deltoid muscle as a single dose. | 22 |
| Age ≥65 Years Healthy participants 65 years and older received 0.5 ml of the trivalent Influenza vaccine (TIV) administered via the intramuscular route in the deltoid muscle as a single dose. | 44 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 4 |
Baseline characteristics
| Characteristic | Age 25-40 Years | Age ≥65 Years | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 44 Participants | 44 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 0 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 41 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 40 Participants | 52 Participants |
| Region of Enrollment United States | 22 participants | 44 participants | 66 participants |
| Sex: Female, Male Female | 14 Participants | 23 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 21 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 22 | 29 / 44 |
| serious Total, serious adverse events | 0 / 22 | 1 / 44 |
Outcome results
Primary
Efficacy, Measured by the Number of Subjects With a Change in Innate Immune Signatures
The number of subjects with a change in innate immunity signatures correlating with the level of antibodies was recorded. The innate immune signatures were assessed by Fluorescence Activated Cell Sorting (FACS)/Luminex assays. The levels of antibodies to the influenza virus prior to TIV (trivalent influenza vaccine) administration and on Day 180 after receiving TIV was assessed and the number of subjects who exhibited an increase in the antibodies and, therefore, a change in their innate immune signatures, was recorded.
Time frame: Day 0 (prior to TIV administration), Day 180 (from the time of of TIV administration)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 25-40 Years | Efficacy, Measured by the Number of Subjects With a Change in Innate Immune Signatures | 22 participants |
| Age ≥65 Years | Efficacy, Measured by the Number of Subjects With a Change in Innate Immune Signatures | 44 participants |
Secondary
Number of Participants With Specific B Cell Responses That Correlate With the Innate Immune Signatures
The secondary outcomes will identify the number of participants with a positive B cell response to the flu shot particulary looking for antibody responses, presence of plasmablasts, antibody repertoire.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 25-40 Years | Number of Participants With Specific B Cell Responses That Correlate With the Innate Immune Signatures | 21 participants |
| Age ≥65 Years | Number of Participants With Specific B Cell Responses That Correlate With the Innate Immune Signatures | 40 participants |