Immune Response to Pneumococcal Vaccination in HIV Infected Individuals

Pneumococcal Infection Clinical Trial

Official title:

Immune Response to Pneumococcal Vaccination in HIV Infected Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02515240
• Other study ID #: HIV PPV23
• Secondary ID: 5R01AI081558
• Status: Completed
• Phase: Phase 0
• First received: July 7, 2015
• Last updated: August 5, 2015
• Start date: July 2010
• Est. completion date: March 2015

Study information

• Verified date: July 2015
• Source: University of Toledo Health Science Campus
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study. To characterize the immune response to the pneumococcal vaccine in HIV positive individuals and to dissect the most appropriate timing and frequency of vaccination.

Description:

All potential study candidates will be asked to fill out a questionnaire concerning their medical history and medications. This survey will determine eligibility. If eligible, as part of the experimental protocol the HIV positive participants will agree to be randomized to immediate vs. delayed pneumococcal immunization and 3 blood draws around the time of immunization. The HIV negative control population will agree to immunization with pneumococcal polysaccharide vaccine (PPV), not standard of care for this population, and 3 blood draws around the time of immunization. The investigators will study the effect of pneumococcal vaccination in HIV positive adults. At the present time it is recommended that all HIV positive individuals receive the pneumococcal vaccine at the time of diagnosis with those with cluster of differentiation (CD4) count <200 to be vaccinated either immediately or alternatively, treated with highly active antiretroviral therapy (HAART) for 6 months followed by PPV. All patients are recommended to be re-vaccinated at 5 years. This is the standard of care. It is however unclear how the HIV positive patients respond to PPV. In the 1st part of the study, Part I, newly diagnosed HIV positive individuals will be recruited. As standard of care, these individuals will receive the pneumococcal vaccine regardless of their participation in this study. Those that agree to participate in the study will be grouped according to their CD4 count: >500, 200-500 or <200. Those with a CD4 count <200 will be randomly assigned to receive the vaccine immediately or to receive HAART for 6 months prior to vaccination, this is in accordance with the present recommendations, either immediate vaccination or giving HAART for 6 months prior to vaccination is considered acceptable.. Thus ALL HIV positive individuals will receive the vaccine as presently recommended. The HIV positive volunteers agree to (experimental part of the protocol):

1. Be randomized to either immediate vaccination vs. 6 months after start of HAART if the CD4 count is <200

2. Donate blood specimens at 3 different times: day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL.

3. Have their blood samples subjected to antibody analysis (concentration and functional activity) and antibody gene usage analysis There will be 4 HIV positive groups in this part of the study: CD4>500, CD4 200-500, CD4 < 200 immediate vaccination and CD4 <200, delayed vaccination.

There will be 19 individuals per group. The HIV negative controls in Part I of the study (n=19) who agree to participate will also be vaccinated with the pneumococcal vaccine. This is NOT a vaccine recommended for healthy adults but is NOT contra-indicated.

Thus as part of the experimental procedure for these individuals they will:

1. Receive the FDA approved pneumococcal vaccine

2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42, one time sample of 2 mL.

3. Blood samples will be analyzed for antibody concentration, functional activity and gene family usage.

In summary, we will study a total of 5 groups in Part I:

Group 1: HIV positive CD4>500 Group 2: HIV positive CD4 200-500 Group 3: HIV positive CD4 < 200 immediate vaccination Group 4: HIV positive CD4<200 delayed (6 months) vaccination Group 5: HIV negative In part II of the study the investigators will evaluate the effect of a second pneumococcal vaccination, which is presently recommended, in HIV positive individuals, to be received 5 years after the first vaccination. Again, only those HIV positive individuals who are due for their second pneumovax will be asked to participate. They will be grouped according to their CD4 counts as CD4 >500 or CD4 200-500. Thus ALL HIV positive individuals will receive the vaccine as recommended.

The HIV positive volunteers solely agree to;

1. Donate blood specimens at 3 different occasions: day 0, day of vaccination: 2 mL, at day 7, 40 mL and at day 28-42 a one time sample of 2 mL.

2. Have their blood samples subjected to antibody analysis (concentration and functional activity) and antibody gene usage analysis There will be 2 HIV positive groups: CD4>500 and CD4 count 200-500. There will be 19 individuals per group.

The HIV negative controls in Part II of the study who agree to participate will be recruited from the population of individuals previously vaccinated with pneumovax. They will also be vaccinated for the second time with the pneumococcal vaccine, 5 years after the first vaccination. This is NOT a vaccine recommended for healthy adults but is NOT contra-indicated. Thus as part of the experimental procedure for these individuals they will:

1. Receive the FDA approved pneumococcal vaccine

2. Blood samples will be obtained at day 0: 2 mL, day 7 40 mL and day 28-42 one time sample of 2 mL.

3. Blood samples will be analyzed for antibody concentration, functional activity and gene family usage.

In summary, we will study 3 groups in Part II of the study Group 6: HIV positive CD4>500, 2nd PPV Group 7: HIV positive CD4 200-500, 2nd PPV Group 8: HIV negative, 2nd PPV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: March 2015
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 19 Years to 65 Years

Eligibility

Inclusion Criteria:

• HIV negative:

• never immunized with PPV23

• HIV positive:

• need for PPV23 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:
• PPV23
23 valent pneumococcal polysaccharide vaccine in Healthy adults.

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 Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (16)

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

Berberian L, Goodglick L, Kipps TJ, Braun J. Immunoglobulin VH3 gene products: natural ligands for HIV gp120. Science. 1993 Sep 17;261(5128):1588-91. — View Citation

Berberian L, Shukla J, Jefferis R, Braun J. Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo. J Acquir Immune Defic Syndr. 1994 Jul;7(7):641-6. — View Citation

Chang Q, Abadi J, Alpert P, Pirofski L. A pneumococcal capsular polysaccharide vaccine induces a repertoire shift with increased VH3 expression in peripheral B cells from human immunodeficiency virus (HIV)-uninfected but not HIV-infected persons. J Infect — 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

Karray S, Zouali M. Identification of the B cell superantigen-binding site of HIV-1 gp120. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1356-60. — 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

Loeliger AE, Rijkers GT, Aerts P, Been-Tiktak A, Hoepelman AI, van Dijk H, Borleffs JC. Deficient antipneumococcal polysaccharide responses in HIV-seropositive patients. FEMS Immunol Med Microbiol. 1995 Sep;12(1):33-41. — View Citation

Müller S, Köhler H. B cell superantigens in HIV-1 infection. Int Rev Immunol. 1997;14(4):339-49. Review. — View Citation

Ochs HD, Junker AK, Collier AC, Virant FS, Handsfield HH, Wedgwood RJ. Abnormal antibody responses in patients with persistent generalized lymphadenopathy. J Clin Immunol. 1988 Jan;8(1):57-63. — View Citation

Opravil M, Fierz W, Matter L, Blaser J, Lüthy R. Poor antibody response after tetanus and pneumococcal vaccination in immunocompromised, HIV-infected patients. Clin Exp Immunol. 1991 May;84(2):185-9. — View Citation

Ragni MV, Ruben FL, Winkelstein A, Spero JA, Bontempo FA, Lewis JH. Antibody responses to immunization of patients with hemophilia with and without evidence of human immunodeficiency virus (human T-lymphotropic virus type III) infection. J Lab Clin Med. 1 — 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

Townsley-Fuchs J, Neshat MS, Margolin DH, Braun J, Goodglick L. HIV-1 gp120: a novel viral B cell superantigen. Int Rev Immunol. 1997;14(4):325-38. Review. — View Citation

Unsworth DJ, Rowen D, Carne C, Sonnex C, Baglin T, Brown DL. Defective IgG2 response to Pneumovax in HIV seropositive patients. Genitourin Med. 1993 Oct;69(5):373-6. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody activity and response by opsonophagocytic assay (OPT) and ELISA (ug/ml)		Day 0 and day 30 of vaccination	No
Secondary	Polysaccharide-specific B cell phenotype: percentage naive or memory B cell distribution flow cytometry		Day 0 and Day7 of vaccination	No
Secondary	Flow cytometry : percentage cells expressing tumor necrosis factor receptors on surface		Day 0 and Day7 of vaccination	No