Clinical trial NCT01232868: Systems Biology of Trivalent Influenza Vaccine (TIV) in Young and Elderly
Official title: Systems Biology of Trivalent Influenza Vaccine (TIV) in Young and Elderly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Influenza
Keywords: Innate immunity
Adaptive immunity
Slu shot
Elderly
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2010-11-02
Enrollment: 66
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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 \[i.e. more than 10 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 3 months\*; receipt of high-dose inhaled steroids is also an exclusion criteria (nasal and topical steroids are allowed.)\], congenital immunodeficiency, anatomical or functional asplenia.
   * Pregnancy or breast feeding
4. Conditions that could affect the safety of the volunteers such as:

   * Severe reactions to prior vaccination with TIV, including anaphylaxis.
   * History of Guillain Barré syndrome
   * History of bleeding disorders
   * Any allergy to any component of the vaccine including egg allergy.
5. Volunteers with any acute illness, including any fever (\> 100.4 F \[\> 38.0C\], regardless of the route) within 3 days prior to study entry \*.
6. Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.

   * Note:

An individual who initially is excluded from study participation based on one or more of the time-limited exclusion criteria (e.g., acute illness, receipt or expected receipt of live or inactivated vaccines ) may be reconsidered for enrollment once the condition has resolved as long as the subject continues to meet all other entry criteria.

Subjects receiving \> 10 mg/day of prednisone or its equivalent daily or on alternate days for more than 2 weeks may enter the study after therapy has been discontinued for more than 3 months.

Primary outcomes:
measure: Efficacy, Measured by the Number of Subjects With a Change in Innate Immune Signatures
timeFrame: Day 0 (prior to TIV administration), Day 180 (from the time of of TIV administration)
Secondary outcomes:
measure: Number of Participants With Specific B Cell Responses That Correlate With the Innate Immune Signatures
timeFrame: 2 years
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Hope Clinic of the Emory Vaccine Center
state: Georgia
Study officials:
affiliation: Emory University
name: Nadine Rouphael, MD
role: PRINCIPAL_INVESTIGATOR
References: