Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

NCT03104075 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 16-071J-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumonia; Aging

Keywords

Genomics; Epigenomics; Pneumococcal vaccine; Elderly

Outcome Measures

Primary Outcomes (2)

• Pneumococcal-specific Antibody Responses

  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

  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 Outcomes (2)

• Number of Genes Upregulated Following Vaccination With PCV13 or PPSV23

  10 days post first vaccination

• Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23

  baseline and 10 days post first vaccination

Study Arms (2)

Prevnar 13

ACTIVE COMPARATOR

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

Pneumovax 23

ACTIVE COMPARATOR

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

Interventions

Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein 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

Also known as: Prevnar 13

Prevnar 13

Pneumococcal Vaccine Polyvalent 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

Also known as: Pneumovax 23

Pneumovax 23

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• The Jackson Laboratory: lead
• UConn Health: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (1)

UConn Center On Aging

Farmington, Connecticut, 06030, United States

Location

Related Publications (2)

• 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.

  PMID: 34465366 BACKGROUND

• 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.

  PMID: 37131707 RESULT

MeSH Terms

Conditions

Pneumonia

Interventions

13-valent pneumococcal vaccine; Pneumococcal Vaccines; 23-valent pneumococcal capsular polysaccharide vaccine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Jacques Banchereau
• Organization: The Jackson Laboratory

jacques.banchereau@jax.org

860-837-2443

Study Officials

• George Kuchel, M.D. F.R.C.P

  UConn Center on Aging

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized assignment to group will be in a 1:1 ratio utilizing block randomization in blocks of 10 to receive Prevnar-13 or Pneumovax 23. Following randomized assignment of vaccine, the study will be open-label.

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: April 7, 2017
• Study Start: April 17, 2017
• Primary Completion: December 5, 2019
• Study Completion: August 29, 2020
• Last Updated: August 22, 2025
• Results First Posted: December 7, 2021

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Conclusion of study
• Access Criteria: GEO open access Raw IPD controlled-access dbGaP per accession number above.

Locations

US (1)