Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

The Jackson Laboratory

Status and phase: Completed; Phase 4

Conditions: Aging; Pneumonia

Treatments: Biological: Pneumococcal Vaccine Polyvalent; Biological: Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein

Study type: Interventional

Funder types: Other

Identifiers

NCT03104075

16-071J-1

Details and patient eligibility

About

This is a prospective, single-site, randomized, then open-label study designed to develop a detailed transcriptional and epigenetic profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults.

In this study, 40 healthy adults ages 60 and older that have never received pneumococcal vaccination, will be randomized in a 1:1 ratio to receive Prevnar-13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Following randomized assignment of vaccine, the study will be open-label.

Six (6) study visits will occur over about 70 days, with an optional 7th visit for participants to receive a second vaccination with the other pneumococcal vaccine one to two years after randomization. Participants will provide blood samples for transcriptional, epigenetic and biological analyses pre- and post-vaccination.

Full description

This prospective, single-site, randomized, then open-label study is designed to develop a detailed transcriptional and epigenetic profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults. This knowledge may lead to development of more effective vaccines through increased understanding of the effects of immunosenescence on mechanisms of immune response to pneumococcal vaccination in older adults elderly.

Forty (40) healthy adults ages 60 and older that have never received pneumococcal vaccination, will be randomized in a 1:1 ratio to receive Prevnar-13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Following randomized assignment of vaccine, the study will be open-label. The study sample will be drawn from the population of healthy older participants in the catchment area of UConn Health in Farmington, CT.

The first six (6) study visits are planned to occur over 67 days at Days -7, 0, 1, 10, 28 (±3 d) and 60 (± 5d). Participants will provide blood samples for transcriptional, epigenetic and biological analyses pre- and post-vaccination.

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with the vaccine that they did not receive by random assignment at Visit 2 (Day 0). This second vaccine will be provided at no charge to the participant. Administration of this vaccine will occur at an optional Visit 7 for participants who choose to receive the second vaccine and will be scheduled at the participant's convenience one-two years after receiving the first pneumococcal vaccine.

If the participant opts to receive the second vaccine within the study and attends optional Visit 7, blood samples for genomic and biologic analysis will be collected at the visit.

Enrollment: 40 patients

Sex: All

Ages: 60+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Able and willing to provide written informed consent
• Male or Female, 60 years of age or older
• Willing to receive pneumococcal vaccination with Prevnar 13 (Wyeth/ Pfizer) or Pneumovax 23 (Merck), as randomly assigned.
• Available to attend 6 study visits over 67 days (Visit 7 is optional at Day 365-720).

Exclusion criteria

• Previous pneumococcal vaccination with Prevnar 13 or Pneumovax 23.

• History of anaphylactic/anaphylactoid or severe allergic reaction to any component of Pneumovax 23, Prevnar 13 or any diphtheria toxoid-containing vaccine.

• Established diagnosis of diabetes

• History of receiving Zostavax (shingles vaccine) within previous 4 weeks. (Study entry may be delayed to satisfy a 28-day interval between vaccinations)

• Known history of any of the following co-morbid conditions:

  • Malignancy (participants without a recurrence in the last 5 years will be allowed)
  • Congestive Heart Failure
  • Cardiovascular Disease (unstable ≤ 6 months*)
  • Kidney disease
  • Renal failure
  • Impaired hepatic function
  • Autoimmune disease such as: Rheumatoid Arthritis, systemic lupus erythematosus (SLE), Inflammatory Bowel Disease, etc.
  • Use of medicines during past 6 months known to alter immune response such as high-dose corticosteroids
  • HIV, AIDS or other Immunodeficiency
  • Recent (≤ 3 months) trauma or surgery
  • Current substance and/or alcohol abuse * Unstable disease is defined as a change in therapy or hospitalization for worsening disease.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Prevnar 13

Active Comparator group

Description:

Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care.

Treatment:

Biological: Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein

Pneumovax 23

Active Comparator group

Description:

Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care.

Treatment:

Biological: Pneumococcal Vaccine Polyvalent