Systems Biology of 23-valent Pneumococcal Polysaccharide Vaccine (PNEUMOVAX®23) and 13-valent Pneumococcal Conjugate Vaccine (PREVNAR 13®)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nadine Rouphael, Emory University
ClinicalTrials.gov Identifier:
NCT01307449
First received: March 1, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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 two FDA approved licensed pneumococcal vaccines between a younger and an older group. Twenty two healthy volunteers between the age of 25-40 and sixty six healthy volunteers between the ages of 60-89 will be enrolled in the study. Each participant in the study will be given one pneumococcal 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.


Condition Intervention
Pneumococcal Infection
Biological: PNEUMOVAX and PREVNAR
Biological: Pneumovax or Prevnar

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Systems Biology of 23-valent Pneumococcal Polysaccharide Vaccine (PNEUMOVAX®23) and 13-valent Pneumococcal Conjugate Vaccine (PREVNAR 13®)

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Number of participants with innate immunity signatures that correlate with the quality of antibodies after PNEUMOVAX and PREVNAR [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The primary outcomes will identify the number of participants with innate immunity signatures in the young and older groups that correlate with the quality of antibodies produced after PNEUMOVAX and PREVNAR


Secondary Outcome Measures:
  • Number of participants with specific B cell responses that correlate with the innate immune signatures after PNEUMOVAX and PREVNAR [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The secondary outcomes will identify the number of participants with a positive B cell response to PNEUMOVAX and PREVNAR particularly looking at the antibody repertoire, quantity of antibodies and plasmablasts


Estimated Enrollment: 88
Study Start Date: April 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Older Group
Participants between the ages of 60-89
Biological: PNEUMOVAX and PREVNAR
Give either 1 dose of PNEUMOVAX or PREVNAR to all participants
Other Names:
  • 23-valent polysaccharide pneumococcal vaccine
  • 13- valent conjugate pneumococcal vaccine
Biological: Pneumovax or Prevnar
Receipt of one vaccination at D0
Experimental: Younger Group
Participants between the ages of 25-40 years
Biological: PNEUMOVAX and PREVNAR
Give either 1 dose of PNEUMOVAX or PREVNAR to all participants
Other Names:
  • 23-valent polysaccharide pneumococcal vaccine
  • 13- valent conjugate pneumococcal vaccine
Biological: Pneumovax or Prevnar
Receipt of one vaccination at D0

Detailed Description:

RATIONALE: PCV13 [13-valent pneumococcal conjugate vaccine (Prevnar®13)] induces better functional immune responses when compared to PPV23 [23-valent pneumococcal polysaccharide vaccine (Pneumovax®23)] in older naïve adults. We hypothesize that this is due to intrinsic defects in innate responses that could explain the poor immunogenicity of PPV23 when compared to PCV13. Therefore, we propose to extensively study innate and adaptive immune responses generated after administration of either pneumococcal polysaccharide or conjugate vaccines in older adults.

STUDY DESIGN: Single center, open label study in which adult healthy volunteers will be vaccinated with either PPV23 or PCV13. Blood samples will be collected on Days D0 (at enrollment) and D1, D3, D7, D14, D30 and D180 post vaccination to study innate and adaptive immune responses.

Even though PPV23 and PCV13 are considered safe, volunteers will be asked to report any local or systemic AEs from Day 0 (vaccination) to Day 7 . Reactogenicity events will also be evaluated by injection site examination on visits at D0, D1, D3 and D7. Also volunteers are asked to report any local or systemic AEs for 30 days post vaccination and any SAEs for 180 days post vaccination. Volunteers are also asked to report local and systemic AEs developing the day of a blood draw.

  Eligibility

Ages Eligible for Study:   25 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Able to understand and give informed consent.
  2. Immunocompetent community dwelling subjects between the ages of ages of 25-40 and 60-89 years.

Exclusion Criteria:

  1. Prior vaccination with pneumococcal vaccine.
  2. Receipt of any of the following products:

    1. Blood products within 3 months prior to study entry or expected receipt at any time after study entry*.
    2. Any live virus vaccines within 4 weeks prior to study entry or expected receipt within 4 weeks after study entry*.
    3. Any inactivated vaccine within 2 weeks or expected receipt within 2 weeks after study entry*.
  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, cerebrospinal fluid leaks, severe kidney disease, autoimmune diseases, severe gastrointestinal diseases and grade 4 hypertension per CTCAE criteria** .
    • Alcohol, drug abuse or 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 known chronic infections including, but not limited, to known HIV, hepatitis B or C; organ transplant; immunosuppression due to cancer; current and/or expected receipt of chemotherapy, radiation therapy, steroids*** (i.e., more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more in the past 90 days , or high dose inhaled corticosteroids**** or any other immunosuppressive therapies (including anti-TNF therapy), functional or anatomic asplenia and congenital immunodeficiency.
  4. Conditions that could affect the safety of the volunteers such as:

    o Severe reactions to prior vaccinations.

    o An allergy to any component of the study vaccines (phenol, aluminum, CRM197 protein, succinic acid, Polysorbate 80).

    • History of Guillain-Barré syndrome.
    • History of bleeding disorders.
  5. Volunteers with any acute illness* including, but not limited to, - fever (> 100.4 F [> 38 C], regardless of the route) within 3 days prior to study entry.
  6. Volunteers with social conditions or occupational conditions or any condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.
  7. Pregnant or breast feeding or women expected to conceive within 30 days after vaccination *****

    • 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.

      • Grade 4 hypertension per CTCAE criteria is defined as Life threatening consequences(e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis) urgent intervention indicated. ***Subjects receiving > 20 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.

        • High dose ICS is defined as: > 960 mcg/day of beclomethasone dipropionate or equivalent ***** 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 receiving PPV23 or PCV13.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307449

Contacts
Contact: Nadine Rouphael, MD 4046861000 ext 16509 nroupha@emory.edu
Contact: Aneesh Mehta, MD 4046861000 ext 16927 aneesh.mehta@emory.edu

Locations
United States, Georgia
Hope Clinic of the Emory Vaccine Center Recruiting
Decatur, Georgia, United States, 30030
Contact: Mary Bower, RN    404-712-1370    mbbower@emory.edu   
Principal Investigator: Nadine Rouphael, MD         
Principal Investigator: Aneesh Mehta, MD         
Sub-Investigator: Mark Mulligan, MD         
Sub-Investigator: Srilatha Edugupanti, MD         
Sub-Investigator: Allison beck, PA         
Sub-Investigator: Colleen Kelley, MD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Nadine Rouphael, MD Emory University
  More Information

No publications provided

Responsible Party: Nadine Rouphael, MD, Emory University
ClinicalTrials.gov Identifier: NCT01307449     History of Changes
Other Study ID Numbers: IRB00047973, U19AI090023
Study First Received: March 1, 2011
Last Updated: May 29, 2014
Health Authority: United States: Federal Government

Keywords provided by Emory University:
pneumococcal vaccine
immune responses

Additional relevant MeSH terms:
Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on September 15, 2014