Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

NCT ID: NCT03104075

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-17
• Study Completion Date: 2020-08-29

Brief Summary

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.

Detailed 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.

Conditions

Pneumonia; Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Prevnar 13

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.

Group Type: ACTIVE_COMPARATOR

Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein

Intervention Type: BIOLOGICAL

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23

Pneumovax 23

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

Group Type: ACTIVE_COMPARATOR

Pneumococcal Vaccine Polyvalent

Intervention Type: BIOLOGICAL

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13

Interventions

Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23

Intervention Type: BIOLOGICAL

Pneumococcal Vaccine Polyvalent

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevnar 13; Pneumovax 23

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

UConn Health

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

The Jackson Laboratory

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Kuchel, M.D. F.R.C.P

Role: PRINCIPAL_INVESTIGATOR

UConn Center on Aging

Locations

UConn Center On Aging

Farmington, Connecticut, United States

Countries

United States

References

Thibodeau A, Eroglu A, McGinnis CS, Lawlor N, Nehar-Belaid D, Kursawe R, Marches R, Conrad DN, Kuchel GA, Gartner ZJ, Banchereau J, Stitzel ML, Cicek AE, Ucar D. AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data. Genome Biol. 2021 Sep 1;22(1):252. doi: 10.1186/s13059-021-02469-x.

Reference Type: BACKGROUND

PMID: 34465366 (View on PubMed)

Ravichandran S, Erra-Diaz F, Karakaslar OE, Marches R, Kenyon-Pesce L, Rossi R, Chaussabel D, Pascual V, Palucka K, Paust S, Nahm MH, Kuchel GA, Banchereau J, Ucar D. Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults. medRxiv [Preprint]. 2023 Apr 19:2023.04.16.23288531. doi: 10.1101/2023.04.16.23288531.

Reference Type: RESULT

PMID: 37131707 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

16-071J-1

Identifier Type: -

Identifier Source: org_study_id