Sequential Versus Simultaneous Pneumococcal Vaccination in Elderly: Immunological Memory and Antibody Levels

Sequential Versus Simultaneous Vaccination With Pneumococcal Conjugate Vaccine (Prevenar 13) and Pneumococcal Polysaccharide Vaccine (Pneumovax 23) in Elderly: Immunological Memory and Antibody Levels

The purpose of the present study is to compare the immunological response of pneumococcal serotype specific B-cells, the humoral immune response and safety after sequential vaccination versus simultaneous vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) versus single vaccination with PPV23 in a prospective, randomized controlled monocentric head-to head clinical study in elderly. The hypothesis of this study is that simultaneous vaccination with PCV13 and PPV23 might achieve an improved immune-response compared to sequential vaccination or single vaccination.

Adults >=60 years without previous pneumococcal vaccination will be randomized in three groups and receive either PCV13 on day 0 plus PPV23 6 months later (sequential vaccination) or they receive PCV13 plus PPV23 simultaneous on day 0 (simultaneous vaccination) or they receive PPV23 on day 0 (single vaccination). Blood will be taken for pneumococcal serotype-specific B-memory cells against four vaccine-serotypes (ST), included in PCV13 and PPV23, vaccine-serotype 3 (ST3), vaccine-serotype 14 (ST14), vaccine-serotype 19A (ST19A) and vaccine-serotype 23F (ST23F) at visit 1, 2,4,5,7 and 8 and for antibody levels against the 12 vaccine-serotypes included in PCV13 and PPV23 at visit 1, 3, 4, 6, 7 and 8 in all three groups. Adverse events will be recorded for 28 days after each vaccination.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Drug: PCV13; Drug: PPV23

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany
    • Center of Infectious Diseases and Infection Control, Jena University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Unvaccinated adults >= 60 years
• Written informed consent

Exclusion Criteria:

• Hypersensitivity against substances included in both vaccines
• Previous pneumococcal vaccination
• Pneumonia within the last two months
• Active infection
• Autoimmune disease
• Ongoing or planned immunosuppressive therapy (including corticosteroid treatment with prednisolon equivalent dose >= 5 mg/d)
• Active malignant disease
• Drug abuse or alcoholic abuse
• Expectation of life < 2 years
• Coagulation disorders
• Burns or injury on the injection site
• Plegia or paresis of extremity where injection is planned
• Shock
• parallel participation in other clinical trial with intervention
• Infusion of blood products within the last half year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sequential vaccination PCV13 and PPV23; PCV13 0.5 ml intramuscular injection once on day 0 PPV23 0.5 ml intramuscular injection once 6 months later	Drug: PCV13; Intramuscular injection of 13-valent pneumococcal conjugate vaccine once; Other Names: Prevenar 13; Drug: PPV23; Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once; Other Names: Pneumovax (MSD)
Experimental: Simultaneous vaccination PCV13 and PPV23; PCV13 0.5ml intramuscular injection once on day 0 followed by PPV23 0.5ml intramuscular injection on day 0	Drug: PCV13; Intramuscular injection of 13-valent pneumococcal conjugate vaccine once; Other Names: Prevenar 13; Drug: PPV23; Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once; Other Names: Pneumovax (MSD)
Active Comparator: Single vaccinationPPV23; PPV23 0.5ml intramuscular injection on day 0	Drug: PPV23; Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once; Other Names: Pneumovax (MSD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response of B-memory cells	Change of immune response of B memory cells against 4 pneumococcal serotypes ST3,ST14,ST19A und ST23F compared to day 0 will be determined by multiparameter flow cytometry. Pneumococcal specific B-cells will be identified by labeling with fluorochrome-coupled polysaccharide antigen, B-memory cells will be identified by expression of characteristic membrane proteins and quantified.	27-28 weeks after first vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response of B-memory cells	Change immune response of B memory cells against 4 pneumococcal serotypes ST3,ST14,ST19A und ST23F compared to day 0 will be determined by multiparameter flow cytometry. Pneumococcal specific B-cells will be identified by labeling with fluorochrome-coupled polysaccharide antigen, B-memory cells will be identified by expression of characteristic membrane proteins and quantified.	1-2 weeks, 26 weeks, 52 weeks, 104 weeks
Humoral immune response	Change of serotype-specific immunoglobulin G concentrations against 12 pneumococcal vaccine-serotypes included in both vaccines PCV13 and PPV23 compared to day 0	4 weeks, 26 weeks, 30 weeks, 52 weeks, 104 weeks
Safety (Adverse events and serious adverse events)	Adverse events and serious adverse events	28 days after each vaccination

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Investigators: Principal Investigator: Mathias Pletz, MD, PhD, University Hospital of Jena, Center of Infectious Diseases and Infection Control

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2017
• Primary Completion (Actual): November 7, 2022
• Study Completion (Actual): November 6, 2023

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimated): December 22, 2015

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: conjugate vaccine; polysaccharide vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: EudraCT 2014-004013-85

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No