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.

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.

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.

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).

Conclusion of study

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

One participant was not included in the baseline data analysis because their blood serum samples were not collected. As a result, the researchers were not able to calculate the baseline OPA titers for this participant to include them in further data analysis.

Data were collected on participants during the 2017-2018 vaccination seasons. Blood samples obtained 7 days prior to vaccination and Day 1, 10, 28, 60 post-vaccination.

AEs were collected on participants throughout the duration of the study. None of the AEs were related to the vaccine. One participant had a vasovagal syncope episode due to blood draw.