Evaluation of PCV21 Vaccination Among PPSV23-experienced, Immunocompromised Elderly Veterans

The investigators will evaluate the immune response of immunocompromised adults, who have previously received at least 1 dose of 23-valent pneumococcal polysaccharide vaccine, to the booster with of 21-valent pneumococcal conjugate vaccine . Immune response will be assessed by opsonophagocytic assay reactivity.

Study Overview

• Status: Not yet recruiting
• Conditions: Immunosuppression; Pneumococcal Vaccines
• Intervention / Treatment: Drug: 21-valent pneumococcal conjugate vaccine

Detailed Description

Recommendations for optimal vaccination strategies in immunocompromised patients has been limited. Strategies focused on utilizing a conjugate vaccine alone, as either initial vaccination or booster dosing, have not demonstrated significant increased antibody expression in immunocompromised patients[7]. Strategies where immunocompromised patients were vaccinated with a conjugate vaccine followed by polysaccharide vaccine have demonstrated that 50% of individuals achieve functional antibodies[7]. Since improved antibody response in naive patients has been seen in combination vaccination, we aim to test this strategy for boosting in previously vaccinated immunocompromised patients. The 15 valent Pneumococcal Conjugate Vaccine (PCV15) is available for use in adults and contains S. Pneumoniae serotypes 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F [5].

In this study we postulate that booster dosing with PCV21 in immunocompromised adults who are at least 5 years from receipt of PPSV23 will elicit a strong immune response represented by change in serotype specific OPA GMT from baseline to 4 weeks post booster vaccine completion. We will specifically evaluate the change in pneumococcal opsonophagocytic activity at baseline to 6 months (Pn-OPA) for S. Pneumoniae serotypes 3, 6A, 15A, 19A, 20A, 23A, 31, 35B, 9n, 11A, and 22F. These specific serotypes have been selected due to current disease burden trends, to address current gaps in data, and have been identified as the most relevant for PCV development underway.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject meets the CDC definition of an immunocompromising condition

  o chronic renal failure, congenital or acquired asplenia, generalized malignancy, HIV infection, Hodgkin disease, iatrogenic immunosuppression, leukemia, lymphoma, multiple myeloma, nephrotic syndrome, sickle cell disease or other hemoglobinopathies, and solid organ transplant.

• Have received at least 1 dose of PPSV23

Exclusion Criteria:

• Less than 5 years since last receipt of PPSV23 validated to patient medical record and Immunize Nevada Website
• Previous administration of PCV20
• Previous administration of PCV13
• Previous administration of PCV15
• Less than 14 days since administration of any COVID19 vaccination
• Previous history of Invasive Pneumococcal Disease (IPD)
• Antibiotic treatment within the previous 90 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: All participants; This will be a single population open label trial evaluating immune response to PCV21 in subjects with immunocompromising conditions or receiving immunosuppressive medications.	Drug: 21-valent pneumococcal conjugate vaccine; FDA approved pneumococcal vaccines 21 valent conjugate vaccine administered at enrollment; Other Names: PCV21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in opsonophagocytic assay (OPA) geometric mean titers (GMT)	Evaluation of the change fold increase in S. Pneumonia OPA GMT from baseline to 24 weeks after the administration of a pneumococcal vaccine booster series consisting of PCV15 followed by PPSV23 8 weeks later for S. Pneumoniae serotypes 1, 3, 4, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F	24 months

Collaborators and Investigators

• Sponsor: VA Sierra Nevada Health Care System
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: immunosuppression; pneumococcal vaccines
• Additional Relevant MeSH Terms: Immunologic Factors; Physiological Effects of Drugs; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 2120135-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data is not planned to be made available at this time.

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.: Yes