Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults

Early Phase 1

Completed

• Conditions: HIV Lipodystrophy; Aging
• Interventions: Biological: Pneumococcal polysaccharide vaccine 23 valent; Biological: 13 valent conjugated pneumococcal vaccine

• Registration Number: NCT03039491
• Lead Sponsor: Medical University of South Carolina

Brief Summary

The investigators hypothesized that pneumococcal vaccination with either the 23-valent pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody levels/functional antibody activity and induce similar pneumococcal polysaccharide (PPS)-specific B cell response in HIV positive individuals \> 50 years of age, HIV positive individuals 21-40 years of age as compared to HIV negative \> 50 years of age. The investigators immunized the study groups HIV+ persons \>50, HIV+ persons 21-40 and controls (HIV negative) with PCV 13 followed by PPV23 and HIV\>50 with PPV alone and examined immune responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody levels and OPA and compared to populations immunized with PPV

Detailed Description

The purpose of this study is to learn more about how older people with HIV respond to the pneumococcal or pneumonia vaccine. Pneumonia occurs very frequently in in older persons AND in persons who are infected with HIV. Therefore, it is common practice to vaccinate against pneumonia in these patient populations. Because older patients with HIV fit both of these categories, it is believed that they are at an increased risk of pneumonia.

There are two types of pneumonia vaccines available for adults approved by the Federal Drug Administration (FDA). One is called the pneumococcal polysaccharide vaccine (PPV23) and protects against 23 different strains of the pneumonia bacteria. The other type of vaccine called the pneumococcal conjugate vaccine (PCV13) protects against different strains of the pneumonia bacteria.

Until 2012, it was recommended that all HIV-positive adults receive PPV23 when diagnosed with HIV and again 5 years later. More recently, the guidelines have changed to all HIV-positive adults are to receive PCV13, followed later with PPV23. At this point in time, it is not clear which regimen works better in aging HIV positive adults. Investigators are doing this study to compare the effectiveness of each vaccine regimen in aging HIV positive adults compared to healthy adults. Although several studies show short-term efficacy or increased antibody response in HIV+ persons with this vaccine, others do not, in either HIV+ population or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV compared to PPV will likely not be conducted, particularly in the aging HIV+ population. It is therefore essential to define immune responses to conjugated and free-polysaccharide preparations by examining traditional antibody and functional levels as well as B cell subsets, critically affected by aging and HIV. Will either PCV or PPV elicit an immune response compatible with protection in this population? Based on persistent B cell perturbations in HAART-treated persons, it is hypothesized that immunization of aging HIV+ persons with PPV23 will be as effective as a PCV13 containing regimen on a quantitative, qualitative, B and T cell level and that the magnitude of this response will be related to the degree of chronic inflammation. The proposed studies are highly significant as they will define the B and T cell responses to a TI-2 and T-cell dependent form of pneumococcal vaccine in the aging HIV+ population. These data will provide the necessary basis for development of a rational vaccination approach, including the potential use of novel adjuvant. In this study the investigators will:

1. Test the hypothesis that vaccination with either PPV alone (TI-2) or a PCV containing regimen (TD) results in similar antibody levels/functional activity, that are determined by levels of chronic inflammation in aging HIV+. The investigators will immunize the study group HIV+ persons 50-65 and controls (HIV+21-40 and HIV- 50-65 years) with PCV13 followed by PPV23 and HIV+ 50-65 and HIV- 50-65 with PPV alone. The investigators will examine immune responses to pneumococcal polysaccharides (PPS) 23 (F), 14, 3, 7 (F) and 19 (A) on a quantitative and qualitative level using ELISA and opsonophagocytic assays (OPA) and correlate the response to the degree of inflammation measured in each participant.

2. To test the hypothesis that the levels of antigen specific B cells identified with PPS will be comparable between the PPV and PCV vaccine recipients. Pre- and post-immunization peripheral blood samples will be obtained. Extensive phenotype analysis using antibodies against cluster of differentiation (CD)19, 20, 21, 27, 38, 40, immunoglobulin M (IgM) , B-cell activating factor (BAFF), trans-membrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antigen (BCMA) markers will be used to characterize PPS-labeled B cells. Specific phenotypes will be correlated with antibody levels, OPA and inflammatory markers and compared to the control populations immunized with PPV.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-09-01
• Study First Submitted: 2017-01-30
• Study First Submitted QC: 2017-01-30
• Study First Posted: 2017-02-01
• Primary Completion: 2020-03-30
• Study Completion: 2020-03-30
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-12
• Last Update Posted: 2020-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

HIV+ 21-40 years of age HIV+ 50-65 years of age HIV- 50-65 years of age

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Exclusion Criteria

• Previous immunization with pneumococcal vaccine less than 5 years ago
• pregnancy and absence of contraceptive practice in women of childbearing age and breast feeding
• known anaphylaxis, hypersensitivity to the pneumonia vaccine
• those who received blood products or gammaglobulin in last 3 months
• inability to comprehend or sihn informed consent
• Medications known to affect immune function (chemotherapy, an angiotensin-converting-enzyme (ACE) inhibitors, corticosteroids, anti-TNFalpha agents)
• previous disease/present illness that may affect response to vaccination: previous pneumococcal disease, removal of spleen, auto-immune disease, end stage renal disease (ESRD) or end stage liver disease, cancer)
• significant (3x upper limit of normal) in complete blood count (CBC), chemistries, immunoglobulin levels

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIV- 50-65, PCV/PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV- individuals , 50-65 years of age immunized with PCV13 followed by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 50-65, CD4>200 PCV/PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 50-65, CD4<200 PCV/PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 50-65 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV- 50-65, PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV- individuals, 50-65 years of age immunized with PPV23 only. Intervention: 23 valent pneumococcal polysaccharide vaccine only
HIV+ 50-65, CD4>200 PCV/PPV	13 valent conjugated pneumococcal vaccine	HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 50-65, CD4<200 PCV/PPV	13 valent conjugated pneumococcal vaccine	HIV+ individuals , 50-65 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 50-65, CD4<200 PCV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 50-65 years of age with a nadir CD4 count \<200 to receive PPV23 only Intervention: 23 valent pneumococcal polysaccharide vaccine only
HIV+ 21-40, CD4>200 PCV/PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 21-40 years of age with a nadir CD4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 21-40, CD4<200 PCV/PPV	13 valent conjugated pneumococcal vaccine	HIV+ individuals , 21-40 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 50-65, CD4>200 PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 50-65 years of age with a nadir CD4 count \>200 to receive PPV23 only Intervention: 23 valent pneumococcal polysaccharide vaccine only
HIV- 50-65, PCV/PPV	13 valent conjugated pneumococcal vaccine	HIV- individuals , 50-65 years of age immunized with PCV13 followed by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 21-40, CD4<200 PCV/PPV	Pneumococcal polysaccharide vaccine 23 valent	HIV+ individuals , 21-40 years of age with a nadir CD4 count \<200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
HIV+ 21-40, CD4>200 PCV/PPV	13 valent conjugated pneumococcal vaccine	HIV+ individuals , 21-40 years of age with a nadir CD4 count \>200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine

Primary Outcome Measures

Name	Time	Method
Antibody response	Change in ug/mL from day 0 to 30 days after receipt of PPV23	Measure antibody response by ELISA (ug/mL)
opsonophagocytic antibody activity	Change in opsonophagocytic titer from day 0 to 30 days after receipt of PPV23	opsonophagocytic antibody response measured by opsonophagocytic assay (OPA)

Secondary Outcome Measures

Name	Time	Method
PPS-specific B cell phenotype	Change from day 56 to day 63 post-vaccination	Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)
Expression of TACI on PPS-specific B cells	change from day 56 to day 63	Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)
Expression of cluster of differentiation 21 (CD21) on PPS-specific B cells	change from day 0 to day 7	Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)
Serum interleukin-6 (IL-6)	Day 0	Measure serum levels IL-6
Expression of BAFFR on PPS-specific B cells	change from day 56 to day 63	Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
Expression of BCMA on PPS-specific B cells	change from day 7 to day 63	Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)
Expression of CD21 on PPS-specific B cells	change from day 56 to day 63	Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)
Expression of CD40 on PPS-specific B cells	change from day 56 to day 63	Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)
Serum APRIL	Day 0	Measure serum levels APRIL
Serum IL-1(B)	Day 0	Measure serum levels IL-1B
Serum IL-8	Day 0	Measure serum levels IL-8
Serum BAFF	Day 0	Measure serum levels BAFF
Serum TNFalpha	Day 0	Measure serum levels TNFalpha
Serum IL-10	Day 0	Measure serum levels IL-10
Serum IL-1(RA)	Day 0	Measure serum levels IL-1RA

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States