Pneumonia Vaccine in Aging HIV Positive Individuals

Pneumococcal Infection Clinical Trial

Official title:

Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02558751
• Other study ID #: RO1-AG045973
• Secondary ID: R01AG045973
• Status: Completed
• Phase: Phase 0
• First received: September 16, 2015
• Last updated: September 23, 2015
• Start date: July 2013
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: University of Toledo Health Science Campus
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pneumococcal Infection
• Pneumococcal Infections

Intervention

Biological:
• 23-valent pneumococcal polysaccharide vaccine
One standard adult dose of the 23-valent pneumococcal polysaccharide vaccine
• 13-valent pneumococcal conjugate vaccine
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.

Locations

Country	Name	City	State
United States	The University of Toledo-Health Science Campus	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Toledo Health Science Campus	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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;1 — View 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. — View 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 pneu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody response measured by ELISA (ug/ml)		Change in ug/ml from day 0 to day 30	No
Primary	Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer)		Change in OPA titer from day 0 to day 30	No
Primary	Antibody response measured by ELISA (ug/ml)		Change in ug/ml from day 0 to day 90	No
Primary	Opsonophagocytic antibody activity measured by opsonophagocytic assay (OPA titer)		Change in OPA titer from day 0 to day 90	No
Secondary	B cell phenotype of PPS-specific B cells expressing CD27+IgM+: flowcytometry (%)		Change from day 0 to day 7 in %	No
Secondary	Serum C-reactive protein (ng/ml)		day 0	No
Secondary	Flow cytometry : percentage cells expressing BAFF-R on surface (%)		Change from day 0 to day 7	No
Secondary	Flow cytometry : percentage cells expressing BAFF-R on surface (%)		Change from day 56 to day 63	No
Secondary	B cell phenotype of PPS-specific B cells expressing CD27IgM: flowcytometry (%)		Change from day 56 to day 63 (%)	No
Secondary	Serum IL-6 level (pg/ml)		Day 0	No
Secondary	Serum sCD27 (U/ml)		Day 0	No
Secondary	Serum sCD30 (U/ml)		Day 0	No
Secondary	Serum BAFF concentration (pg/ml)		Day 0	No
Secondary	Serum TACI concentration (pg/ml)		Day 0	No
Secondary	Serum BCMA concentration (pg/ml)		Day 0	No
Secondary	Flow cytometry : percentage cells expressing CD40 on surface (%)		Change from day 0 to day 7 (%)	No
Secondary	Flow cytometry : percentage cells expressing CD40 on surface (%)		Change from day 56 to day 63 (%)	No
Secondary	Flow cytometry : percentage cells expressing CD21 on surface (%)		Change from day 0 to day 7 (%)	No
Secondary	Flow cytometry : percentage cells expressing CD21 on surface (%)		Change from day 56 to day 63 (%)	No
Secondary	Flow cytometry : percentage cells expressing TACI on surface (%)		Change from day 0 to day 7 (%)	No
Secondary	Flow cytometry : percentage cells expressing TACI on surface (%)		Change from day 56 to day 63 (%)	No