Immunogenicity After Revaccination With 23-valent Pneumococcal Polysaccharide Vaccine: Healthy Elderly People Versus Diabetic Patients

Study Overview
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Brief Summary
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Pneumococcal disease causes thousands of infections, such as meningitis, bloodstream infections, pneumonia, and ear infections in US annually. As pneumococcal vaccines provide serotype-specific protection, it is important to induce sufficient immune responses for the most clinically relevant serotypes. All adults aged 65 years or older are recommended to receive PPSV23 vaccination irrespective of underlying medical conditions. Thus, since May 2013, South Korea introduced PPSV23 in the national immunization program for elderly individuals aged ≥65 years. Following PPSV23 vaccination, serotype-specific IgG concentrations and OPA titers increase and then decline over time thereby decreasing protective efficacy, although these might remain above pre-vaccination levels until 5 years from PPSV23 administration. The decline of pneumococcal immunity may be more prominent among chronically ill patients, including those with diabetes. Currently however, revaccination is not recommended. In this study, we aimed to evaluate the serotype specific immunogenicity between healthy elderly people and old adults with diabetes after revaccination with PPSV23 at the age of 70-75 years. Serotype-specific IgG concentrations and opsonophagocytic killing activity (OPA) titers will be assessed.

Official Title
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Non-randomized Clinical Trial to Compare the Immunogenicity of Revaccination With 23-valent Pneumococcal Polysaccharide Vaccine Between Healthy Elderly and Those With Diabetes in Korea

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Drug: ProDiax-23 (PPSV23)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Elderly people aged 70-75 years Had received PPSV23 in the previous 5-7 years Exclusion Criteria: Immunocompromised patients Subjects receiving immunosuppressive agents Subjects with a history of vaccination with pneumococcal conjugate vaccine Subjects with a history of pneumococcal disease (positive culture from blood or other sterile fluid) Fever (defined as an oral temperature >37.5℃) within 24 h before PPSV23 vaccination

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: healthy old adults aged 70-75 years who received PPSV23<br>Recruitment of 254 healthy 70-75-year healthy old adults who meet the selection and exclusion criteria and voluntarily agree to participate in this study. Vaccination -Based on guidelines for vaccination. Injecting muscles on the triceps Visit 4 weeks after vaccination ․ Blood sample collection for evaluation of immunogenicity (10 mL) ․ Comparison of GMT and seroconversion rates of IgG antibody titers against 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F and 23F) -Comparison of GMT and seroconversion rates of opsonophagocytic killing assay (OPA) for four pneumococcal serotypes (serotypes 5, 6B, 18C, 19A) | Drug: ProDiax-23 (PPSV23)<br>* diabetic old adults aged 70-75 years who received PPSV23 in previous 5-7 years (Persons 65-70 years old who have been inoculated with PPSV23 and 5-7 years have passed) and healthy old adults aged 70-75 years who received PPSV23 in previous 5-7 years (Persons 65-70 years old who have been inoculated with PPSV23 and 5-7 years have passed)<br>|
| Experimental: old adults who have diabetes mellitus aged 70-75 years who rec<br>Recruitment of 254 healthy 70-75-year diabetic old adults who meet the selection and exclusion criteria and voluntarily agree to participate in this study. Vaccination -Based on guidelines for vaccination. Injecting muscles on the triceps Visit 4 weeks after vaccination ․ Blood sample collection for evaluation of immunogenicity (10 mL) ․ Comparison of GMT and seroconversion rates of IgG antibody titers against 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F and 23F) -Comparison of GMT and seroconversion rates of opsonophagocytic killing assay (OPA) for four pneumococcal serotypes (serotypes 5, 6B, 18C, 19A) | Drug: ProDiax-23 (PPSV23)<br>* diabetic old adults aged 70-75 years who received PPSV23 in previous 5-7 years (Persons 65-70 years old who have been inoculated with PPSV23 and 5-7 years have passed) and healthy old adults aged 70-75 years who received PPSV23 in previous 5-7 years (Persons 65-70 years old who have been inoculated with PPSV23 and 5-7 years have passed)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific immunogenicity assessed by opsonophagocytic killing assay. | After PPSV23 vaccination, blood samples (10 mL) will be collected before vaccination and at 4 weeks post-vaccination. Serotype-specific opsonophagocytic activity (OPA) will be evaluated from those blood samples by opsonophagocytic killing assay for 4 serotypes (5, 6B, 18C, 19A). | up to one month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific IgG antibody concentrations assessed by ELISA. | After PPSV23 vaccination, blood samples (10 mL) will be collected before vaccination and at 4 weeks post-vaccination. Serotype-specific IgG antibody concentrations for 13 serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F and 23F) will be measured. | up to one month after vaccination | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Solicited local or systemic reactions to the vaccines will be monitored using diary cards during the14 days post-vaccination. Participants will be asked to record pain, tenderness and redness diameter at both injection sites and systemic symptoms such as headache, malaise, chills, muscle aches, and arthralgia. Severity will be recorded according to the Food and Drug Administration Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Subjects will be also asked to record any unsolicited adverse event during the 14 days after vaccination. | up to one month after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Streptococcus pneumoniae, Diabetes Mellitus, Immunogenicity, Vaccine, Pneumococcal Vaccines