Clinical trial NCT03039491: Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults
Official title: Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HIV Lipodystrophy
Aging
Keywords: pneumococcal vaccination
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2017-02-01
Enrollment: 160
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Antibody response
timeFrame: Change in ug/mL from day 0 to 30 days after receipt of PPV23
measure: opsonophagocytic antibody activity
timeFrame: Change in opsonophagocytic titer from day 0 to 30 days after receipt of PPV23
Secondary outcomes:
measure: PPS-specific B cell phenotype
timeFrame: Change from day 0 to day 7 post-vaccination
measure: PPS-specific B cell phenotype
timeFrame: Change from day 56 to day 63 post-vaccination
measure: Expression of TACI on PPS-specific B cells
timeFrame: change from day 0 to day 7
measure: Expression of TACI on PPS-specific B cells
timeFrame: change from day 56 to day 63
measure: Expression of BAFFR on PPS-specific B cells
timeFrame: change from day 0 to day 7
measure: Expression of BAFFR on PPS-specific B cells
timeFrame: change from day 56 to day 63
measure: Expression of BCMA on PPS-specific B cells
timeFrame: change from day 0 to day 7
measure: Expression of BCMA on PPS-specific B cells
timeFrame: change from day 7 to day 63
measure: Expression of CD40 on PPS-specific B cells
timeFrame: change from day 0 to day 7
measure: Expression of CD40 on PPS-specific B cells
timeFrame: change from day 56 to day 63
measure: Expression of cluster of differentiation 21 (CD21) on PPS-specific B cells
timeFrame: change from day 0 to day 7
measure: Expression of CD21 on PPS-specific B cells
timeFrame: change from day 56 to day 63
measure: Serum interleukin-6 (IL-6)
timeFrame: Day 0
measure: Serum BAFF
timeFrame: Day 0
measure: Serum APRIL
timeFrame: Day 0
measure: Serum IL-10
timeFrame: Day 0
measure: Serum IL-1(RA)
timeFrame: Day 0
measure: Serum IL-1(B)
timeFrame: Day 0
measure: Serum IL-8
timeFrame: Day 0
measure: Serum TNFalpha
timeFrame: Day 0
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Maria A. Julia Westerink, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Crum-Cianflone NF, Huppler Hullsiek K, Roediger M, Ganesan A, Patel S, Landrum ML, Weintrob A, Agan BK, Medina S, Rahkola J, Hale BR, Janoff EN; Infectious Disease Clinical Research Program HIV Working Group. A randomized clinical trial comparing revaccination with pneumococcal conjugate vaccine to polysaccharide vaccine among HIV-infected adults. J Infect Dis. 2010 Oct 1;202(7):1114-25. doi: 10.1086/656147.
citation: de Roux A, Schmole-Thoma B, Siber GR, Hackell JG, Kuhnke A, Ahlers N, Baker SA, Razmpour A, Emini EA, Fernsten PD, Gruber WC, Lockhart S, Burkhardt O, Welte T, Lode HM. Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory. Clin Infect Dis. 2008 Apr 1;46(7):1015-23. doi: 10.1086/529142.
citation: French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H, Mwaiponya M, Zijlstra EE, Molyneux ME, Gilks CF. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010 Mar 4;362(9):812-22. doi: 10.1056/NEJMoa0903029.
citation: Baxendale HE, Keating SM, Johnson M, Southern J, Miller E, Goldblatt D. The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly. Vaccine. 2010 Jul 5;28(30):4763-70. doi: 10.1016/j.vaccine.2010.04.103. Epub 2010 May 14.
citation: Penaranda M, Payeras A, Cambra A, Mila J, Riera M; Majorcan Pneumococcal Study Group. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults. AIDS. 2010 May 15;24(8):1226-8. doi: 10.1097/QAD.0b013e3283389de5.
citation: Khaskhely N, Mosakowski J, Thompson RS, Khuder S, Smithson SL, Westerink MA. Phenotypic analysis of pneumococcal polysaccharide-specific B cells. J Immunol. 2012 Mar 1;188(5):2455-63. doi: 10.4049/jimmunol.1102809. Epub 2012 Jan 23.
citation: Happe M, Samuvel DJ, Ohtola JA, Korte JE, Westerink MAJ. Race-related differences in functional antibody response to pneumococcal vaccination in HIV-infected individuals. Vaccine. 2019 Mar 14;37(12):1622-1629. doi: 10.1016/j.vaccine.2019.01.084. Epub 2019 Feb 21.