Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

August 6, 2025 updated by: The Jackson Laboratory

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • UConn Center on Aging

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Biological: 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
Other Names:
  • Prevnar 13
Active Comparator: Pneumovax 23
Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care.
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
Other Names:
  • Pneumovax 23

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pneumococcal-specific Antibody Responses
Time Frame: 70 days
To vaccinate healthy older participants with pneumococcal vaccines, collect longitudinal blood samples and assess pneumococcal-specific antibody responses. The unit of measurement used is log2 titer defined as a measure to quantify the overall strength of responses using the sum of all serotype responses. Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.
70 days
Pneumococcal-specific Antibody Responses - Fold Change Post First Vaccination
Time Frame: 70 days

Fold change between the baseline and post first vaccination titers was calculated for each pneumococcal vaccine cohort.

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.
70 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Genes Upregulated Following Vaccination With PCV13 or PPSV23
Time Frame: 10 days post first vaccination

RNA-seq and ATAC-seq to enable quantitative assessment of both coding RNA's and ncsRNA's as well as to resolve the epigenetic landscape of immune cells in the context of vaccine responses. We assessed the number of genes upregulated post first vaccination [PCV13 or PPSV23].

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.
10 days post first vaccination
Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23
Time Frame: baseline and 10 days post first vaccination

Measure of functional status of immune cells in older participants following administration of a single pneumococcal vaccine, Prevnar13 or Pneumovax23, at baseline and 10 days post first vaccination.

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.
baseline and 10 days post first vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Jackson Laboratory

Collaborators

University of Alabama at Birmingham
UConn Health

Investigators

  • Principal Investigator: George Kuchel, M.D. F.R.C.P, UConn Center on Aging

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2017

Primary Completion (Actual)

December 5, 2019

Study Completion (Actual)

August 29, 2020

Study Registration Dates

First Submitted

March 21, 2017

First Submitted That Met QC Criteria

March 31, 2017

First Posted (Actual)

April 7, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2025

Last Update Submitted That Met QC Criteria

August 6, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-071J-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participants will provide or decline consent within the ICF for sharing of their randomly recoded (new code that is different than the study code) genomic data in public and/or controlled access scientific databases. The study database will include a field for whether consent for genomic data sharing was provided or declined by the participant and if consent provided was for public and/or limited access databases. This information will be included in the dataset so that it can be provided to dbGAP (NIH database of Genotypes and Phenotypes) at the conclusion of the study to ensure that the wishes of the participant regarding use of their data and samples are respected.

Raw IPD data is available through dbGAP (phs002361) due to patient privacy concerns.

Genomic summary results and gene expression data are shared on GEO; accession numbers GSE247276 (Bulk) and GSE247277 (scRANSeq).

IPD Sharing Time Frame

Conclusion of study

IPD Sharing Access Criteria

GEO open access Raw IPD controlled-access dbGaP per accession number above.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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