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Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults

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ClinicalTrials.gov Identifier: NCT03039491
Recruitment Status : Recruiting
First Posted : February 1, 2017
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
HIV Lipodystrophy Aging Biological: Pneumococcal polysaccharide vaccine 23 valent Biological: 13 valent conjugated pneumococcal vaccine Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals
Actual Study Start Date : September 1, 2015
Estimated Primary Completion Date : March 30, 2020
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: HIV+ 50-65, CD4>200 PCV/PPV

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

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Biological: 13 valent conjugated pneumococcal vaccine
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
Other Name: Prevnar 13

Experimental: HIV+ 50-65, CD4<200 PCV/PPV

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

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Biological: 13 valent conjugated pneumococcal vaccine
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
Other Name: Prevnar 13

Experimental: HIV+ 50-65, CD4>200 PPV

HIV+ individuals , 50-65 years of age with a nadir CD4 count >200 to receive PPV23 only

Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Experimental: HIV+ 50-65, CD4<200 PCV

HIV+ individuals , 50-65 years of age with a nadir CD4 count <200 to receive PPV23 only

Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Active Comparator: HIV- 50-65, PCV/PPV

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

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Biological: 13 valent conjugated pneumococcal vaccine
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
Other Name: Prevnar 13

Active Comparator: HIV- 50-65, PPV

HIV- individuals, 50-65 years of age immunized with PPV23 only.

Intervention: 23 valent pneumococcal polysaccharide vaccine only

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Active Comparator: HIV+ 21-40, CD4>200 PCV/PPV

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

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Biological: 13 valent conjugated pneumococcal vaccine
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
Other Name: Prevnar 13

Active Comparator: HIV+ 21-40, CD4<200 PCV/PPV

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

Biological: Pneumococcal polysaccharide vaccine 23 valent
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 23 serotypes of Streptococcus pneumoniae
Other Name: Pneumovax

Biological: 13 valent conjugated pneumococcal vaccine
This is the pneumococcal vaccine consisting of the capsular polysaccharides of 13 serotypes of Streptococcus pneumoniae conjugated to non-toxic diphtheria carrier protein 197
Other Name: Prevnar 13




Primary Outcome Measures :
  1. Antibody response [ Time Frame: Change in ug/mL from day 0 to 30 days after receipt of PPV23 ]
    Measure antibody response by ELISA (ug/mL)

  2. opsonophagocytic antibody activity [ Time Frame: 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 :
  1. PPS-specific B cell phenotype [ Time Frame: Change from day 0 to day 7 post-vaccination ]
    Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)

  2. PPS-specific B cell phenotype [ Time Frame: Change from day 56 to day 63 post-vaccination ]
    Measure: B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)

  3. Expression of TACI on PPS-specific B cells [ Time Frame: change from day 0 to day 7 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)

  4. Expression of TACI on PPS-specific B cells [ Time Frame: change from day 56 to day 63 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing TACI on their surface (%)

  5. Expression of BAFFR on PPS-specific B cells [ Time Frame: change from day 0 to day 7 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)

  6. Expression of BAFFR on PPS-specific B cells [ Time Frame: change from day 56 to day 63 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)

  7. Expression of BCMA on PPS-specific B cells [ Time Frame: change from day 0 to day 7 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)

  8. Expression of BCMA on PPS-specific B cells [ Time Frame: change from day 7 to day 63 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing BAFFR on their surface (%)

  9. Expression of CD40 on PPS-specific B cells [ Time Frame: change from day 0 to day 7 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)

  10. Expression of CD40 on PPS-specific B cells [ Time Frame: change from day 56 to day 63 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD40 on their surface (%)

  11. Expression of cluster of differentiation 21 (CD21) on PPS-specific B cells [ Time Frame: change from day 0 to day 7 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)

  12. Expression of CD21 on PPS-specific B cells [ Time Frame: change from day 56 to day 63 ]
    Measure:Flow cytometry: percentage of PPS-specific B cells expressing CD21 on their surface (%)

  13. Serum interleukin-6 (IL-6) [ Time Frame: Day 0 ]
    Measure serum levels IL-6

  14. Serum BAFF [ Time Frame: Day 0 ]
    Measure serum levels BAFF

  15. Serum APRIL [ Time Frame: Day 0 ]
    Measure serum levels APRIL

  16. Serum IL-10 [ Time Frame: Day 0 ]
    Measure serum levels IL-10

  17. Serum IL-1(RA) [ Time Frame: Day 0 ]
    Measure serum levels IL-1RA

  18. Serum IL-1(B) [ Time Frame: Day 0 ]
    Measure serum levels IL-1B

  19. Serum IL-8 [ Time Frame: Day 0 ]
    Measure serum levels IL-8

  20. Serum TNFalpha [ Time Frame: Day 0 ]
    Measure serum levels TNFalpha



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:HIV+ 21-40 years of age HIV+ 50-65 years of age HIV- 50-65 years of age

-

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03039491


Contacts
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Contact: MariaA. Julia Westerink, MD 843-792-9799 westerin@musc.edu
Contact: Myra Happe 843-792-2218 soloshch@musc.edu

Locations
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United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: myra happe    843-792-2218    soloshch@musc.edu   
Sponsors and Collaborators
Medical University of South Carolina
Investigators
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Principal Investigator: Maria A. Julia Westerink, MD Medical University of South Carolina

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT03039491     History of Changes
Other Study ID Numbers: MUSC vaccine study
First Posted: February 1, 2017    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data will be made available once analysis is completed through publications in peer reviewed journals.

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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

Keywords provided by Medical University of South Carolina:
pneumococcal vaccination

Additional relevant MeSH terms:
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Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs