Expired Study
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Toledo, Ohio 43614


Purpose:

The investigators hypothesized that vaccination with either the 23-valent pneumococcal polysaccharide vaccine (PPV23) alone or the 13-valent pneumococcal conjugate vaccine (PCV 13) followed by PPV23 results in similar antibody levels/functional activity and induce a similar pneumococcal polysaccharide (PPS)-specific B cell response in HIV-positive individuals >50 years of age and HIV-negative persons>50 years of age. The investigators immunized the study group HIV+ persons>50 and controls (HIV negative >50 years) with PCV13 followed by PPV23 and HIV+>50 with PPV23 alone. The investigators examined immune responses to PPS23F and PPS14 on a quantitative and qualitative level using ELISA and opsonophagocytic assays (OPA). To test the hypothesis that the levels of antigen specific B cells identified with PPS were comparable between the PPV23 and PCV13 vaccine recipients. 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 historic populations immunized with PPV.


Study summary:

All potential study candidates were asked to fill out a questionnaire concerning their medical history and medications. This survey determined eligibility. If eligible, as part of the experimental protocol the HIV positive participants agreed to be randomized to PPV23 alone versus PCV13 followed 8 weeks later by PPV23 immunization and 3 to 5 blood draws around the time of immunization. The HIV negative control population agreed to immunization with PCV13 followed 8 weeks later by PPV23, not standard of care for this population, and 5 blood draws around the time of immunization. The investigators compared the effect of single dose pneumococcal polysaccharide vaccination versus PCV13 followed by PPV23 vaccination in HIV positive adults. Prior to 2012, the standard of care of HIV positive adults included vaccination with PPV23. In 2012, these recommendations changed and it was recommended that all HIV positive adults be vaccinated with PCV13 followed at least 8 weeks later by PPV23. The benefit of this vaccination protocol over PPV23 alone in HIV positive adults >50 years of age however had not been studied. As part of this study, all HIV positive adults>50 years of age and a CD4 count>200 who were due for pneumococcal vaccination as standard of care, were asked to participate in the study. Those who agreed and were eligible to participate were randomly assigned to receive PCV13 followed at least 8 weeks later with PPV23 or received a single vaccination with PPV23. As standard of care, all individuals who were due for their pneumococcal vaccine and were not eligible for the study received PCV13 followed by PPV23. The HIV positive volunteers (n=37) agreed to (experimental part of the protocol): 1. Be randomized to either vaccination with PCV13 followed by PPV23 OR PPV23 alone. 2. Donate blood specimens at 3-5 different times: PPV23 group:day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL PCV13/PPV23 group: day 0, day of vaccination with PCV13: 2 mL, at day 7, 40 mL and at day 56, day of PPPV23, 2 mL, day 63 a 40 mL sample and finally at day 90 a one time sample of 2 mL. 3. Have blood samples subjected to antibody analysis (concentration and functional activity) and PPS-specific B cell phenotype and tumor necrosis factor receptors (TNFR) . The HIV negative controls in the study (n=14) who agree to participate were vaccinated with the PCV13 followed by PPV23.This is NOT a vaccine regime recommended for healthy adults but is NOT contraindicated. Thus as part of the experimental procedure for these individuals they will: 1. Receive the FDA approved PCV13 and PPV23 2. Blood samples were obtained at day 0, day of vaccination with PCV13: 2 mL, at day 7, 40 mL and at day 56, day of PPPV23, 2 mL, day 63 a 40 mL sample and finally at day 90 a one time sample of 2 mL. 3. Blood samples were analyzed for antibody concentration, functional activity and PPS-specific B cell phenotype and TNFR. In summary,the investigators studied 3 populations, all were between 50-65 years of age: Group 1: HIV positive CD4>200 vaccinated with PPV23 Group 2: HIV positive CD4> 200 vaccinated with PCV13 followed 8 weeks later by PPV23 Group 3: HIV negative vaccinated with PCV13/PPV23.


Criteria:

Inclusion Criteria: - HIV negative: - never immunized with PCV13 - HIV positive: - need for pneumococcal vaccination per standard of care Exclusion Criteria: - steroid use - other immunosuppressive agents; - pregnancy - incapable of completing consent form


Study is Available At:


Original ID:

RO1-AG045973


NCT ID:

NCT02558751


Secondary ID:

R01AG045973


Study Acronym:


Brief Title:

Pneumonia Vaccine in Aging HIV Positive Individuals


Official Title:

Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals


Overall Status:

Completed


Study Phase:

Phase 0


Genders:

Both


Minimum Age:

50 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Toledo Health Science Campus


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificatio


Number of Arms:

3


Number of Groups:

0


Total Enrollment:

51


Enrollment Type:

Actual


Overall Contact Information

Official Name:Maria AJ Westerink, M.D.
Principal Investigator
University of Toledo

Study Dates

Start Date:July 2013
Completion Date:June 2015
Completion Type:Actual
Primary Completion Date:June 2015
Primary Completion Type:Actual
Verification Date:September 2015
Last Changed Date:September 23, 2015
First Received Date:September 16, 2015

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing TACI on surface (%)
Time Frame:Change from day 56 to day 63 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing TACI on surface (%)
Time Frame:Change from day 0 to day 7 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing CD21 on surface (%)
Time Frame:Change from day 56 to day 63 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing CD21 on surface (%)
Time Frame:Change from day 0 to day 7 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing CD40 on surface (%)
Time Frame:Change from day 56 to day 63 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing CD40 on surface (%)
Time Frame:Change from day 0 to day 7 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum BCMA concentration (pg/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum TACI concentration (pg/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum BAFF concentration (pg/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum sCD30 (U/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum sCD27 (U/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum IL-6 level (pg/ml)
Time Frame:Day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:B cell phenotype of PPS-specific B cells expressing CD27IgM: flowcytometry (%)
Time Frame:Change from day 56 to day 63 (%)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing BAFF-R on surface (%)
Time Frame:Change from day 56 to day 63
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Flow cytometry : percentage cells expressing BAFF-R on surface (%)
Time Frame:Change from day 0 to day 7
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Serum C-reactive protein (ng/ml)
Time Frame:day 0
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)
Time Frame:Change from day 0 to day 7 in %
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer)
Time Frame:Change in OPA titer from day 0 to day 90
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Antibody response measured by ELISA (ug/ml)
Time Frame:Change in ug/ml from day 0 to day 90
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer)
Time Frame:Change in OPA titer from day 0 to day 30
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Antibody response measured by ELISA (ug/ml)
Time Frame:Change in ug/ml from day 0 to day 30
Safety Issues:False

Study Interventions

Intervention Type:Biological
Name:23-valent pneumococcal polysaccharide vaccine
Description:One standard adult dose of the 23-valent pneumococcal polysaccharide vaccine
Arm Name:HIV positive PPV23
Other Name:PPV23 or Pneumovax
Intervention Type:Biological
Name:13-valent pneumococcal conjugate vaccine
Description:One dose of the 13-valent pneumococcal conjugate vaccine, PCV13, followed 8 weeks later by one dose of the 23-valent pneumococcal polysaccharide vaccine, PPV23.
Arm Name:HIV positive PCV13/PPV23
Other Name:PCV13 or Prevnar 13

Study Arms

Study Arm Type:Active Comparator
Arm Name:HIV negative PCV13/PPV23
Description:HIV-negative individual 50-65 years of age, Intervention: one dose of 13-valent pneumococcal conjugate vaccine,PCV13, followed 8 weeks later with one dose of 23-valent pneumococcal polysaccharide vaccine, PPV23
Study Arm Type:Active Comparator
Arm Name:HIV positive PCV13/PPV23
Description:HIV-positive individual 50-65 years of age, Intervention: one dose of 13-valent pneumococcal conjugate vaccine,PCV13, followed 8 weeks later with one dose of 23-valent pneumococcal polysaccharide vaccine, PPV23
Study Arm Type:Active Comparator
Arm Name:HIV positive PPV23
Description:HIV-positive individuals 50-65 years of age immunized with one dose of the 23-valent pneumococcal polysaccharide vaccine, PPV23

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Toledo Health Science Campus
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Institute on Aging (NIA)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Rodriguez-Barradas MC, Musher DM, Lahart C, Lacke C, Groover J, Watson D, Baughn R, Cate T, Crofoot G. Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine. J Infect Dis. 1992 Mar;165(3):553-6.
PMID:1347058
Reference Type:Results Reference
Citation:Kroon FP, van Dissel JT, Ravensbergen E, Nibbering PH, van Furth R. Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults. Vaccine. 2000 Nov 22;19(7-8):886-94.
PMID:11115712
Reference Type:Results Reference
Citation:Klein RS, Selwyn PA, Maude D, Pollard C, Freeman K, Schiffman G. Response to pneumococcal vaccine among asymptomatic heterosexual partners of persons with AIDS and intravenous drug users infected with human immunodeficiency virus. J Infect Dis. 1989 Nov;160(5):826-31.
PMID:2572650
Reference Type:Results Reference
Citation:Janoff EN, Douglas JM Jr, Gabriel M, Blaser MJ, Davidson AJ, Cohn DL, Judson FN. Class-specific antibody response to pneumococcal capsular polysaccharides in men infected with human immunodeficiency virus type 1. J Infect Dis. 1988 Nov;158(5):983-90.
PMID:3183430
Reference Type:Results Reference
Citation:Ballet JJ, Sulcebe G, Couderc LJ, Danon F, Rabian C, Lathrop M, Clauvel JP, Seligmann M. Impaired anti-pneumococcal antibody response in patients with AIDS-related persistent generalized lymphadenopathy. Clin Exp Immunol. 1987 Jun;68(3):479-87.
PMID:3652522

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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