Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02012309
Recruitment Status : Recruiting
First Posted : December 16, 2013
Last Update Posted : January 18, 2018
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
HIV infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/AIDS virus itself. Treatment of HIV with antiretroviral medications has decreased the frequency of many complications by over 90%, but bacterial pneumonia remains extremely high. Current vaccines are not very effective in preventing these infections in patients with HIV infection. The investigators are studying the cells (B cells) that make antibodies to fight infection by binding to and killing bacteria. The goal is to understand how HIV impairs the ability of B cells to make antibodies in sufficient quantity and of sufficient quality to protect patients with HIV to learn how to enhance protection against these infections. The investigators also seek to understand the role of the bacteria (specifically Streptococcus pneumoniae) that normally live in the nose and throat in the development of pneumonia and other infections.

Condition or disease Intervention/treatment Phase
HIV Pneumococcal Infections Pneumococcal Vaccines Biological: PCV-13 Biological: PPSV-23 Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Mechanisms of Impaired HIV-associated B Cell and Pneumococcal Vaccine Responses
Study Start Date : August 2014
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arm Intervention/treatment
Experimental: HIV-seronegative
HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0.
Biological: PCV-13
Other Name: Prevnar
Experimental: HIV-infected
HIV-infected subjects will receive Prevnar (PCV-13) at week 0, and Pneumovax (PPSV-23) at week 8 per Advisory Committee on Immunization Practices (ACIP) guidelines.
Biological: PCV-13
Other Name: Prevnar
Biological: PPSV-23
Other Name: Pneumovax

Primary Outcome Measures :
  1. B and T cell subsets [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ]
    Activation and subset distribution of B and T cell subsets and cluster of differentiation positive (CD4+) T cells and T follicular helper (TFH) cells on days 0 and 7 after stimulation

  2. Total IgG, IgM and IgA [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ]
    Total immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) produced from culture of peripheral blood mononuclear cells (PBMC) stimulated in triplicate with B cell stimuli on day 7 by enzyme-linked immunosorbent assay (ELISA)

  3. Antibody-secreting cells [ Time Frame: Weeks 0, 1, 8, 9 ]
    Total IgG, IgM and IgA antibody-secreting cells (ASC) enumerated by enzyme-linked immunospot (ELISPOT) on day 0 and day 7

  4. AID and BCL-6 production [ Time Frame: Weeks -12, 0, 1, 8, 9, 16 ]
    RNA extraction for activation-induced cytidine deaminase (AID) and B cell lymphoma protein 6 (BCL6) expression and mutation from stimulated B cells

Secondary Outcome Measures :
  1. S.pneumoniae colonization and nasopharyngeal microbiome [ Time Frame: Weeks -12, 0, 8, 16 ]
    Prevalence of nasopharyngeal S. pneumoniae determined by quantitative polymerase chain reaction(Q-PCR) and 16S ribosomal RNA (rRNA) sequencing, related microbiota (commensal bacteria) and correlation between colonization and levels of pneumococcal capsule-specific IgG

  2. S.pneumoniae urine antigen positivity [ Time Frame: Week -12 ]
    S. pneumoniae urine antigen positivity in relation to colonization

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

For HIV-infected subjects:

  • adults aged 18-55 years
  • >200 CD4+ T-cells/microliter
  • no antiretroviral therapy (at the time of nasal swab/week 0)
  • receiving antiretroviral therapy for >6 weeks (at the time of vaccination/week 12)

For HIV-seronegative controls:

  • adults aged 18-55 years

Exclusion Criteria:

For all subjects:

  • age <18 or >55 years
  • history of prior pneumococcal vaccination
  • immunosuppressive therapy, defined as: prednisone >15mg/day currently or >14 days in the past 3 months, cytotoxic agents, anti-metabolites, cyclosporine, anti-tumor necrosis factor, B cell monoclonal antibodies
  • current or chronic pulmonary infection (bacterial, fungal, mycobacterial), pneumonia, or rhinosinusitis within 2 months
  • chronic lung disease
  • renal insufficiency, defined as serum creatinine >1.6
  • active liver disease, including hepatitis C virus infection
  • history of splenectomy
  • history of antibacterial therapy within 3 months of nasal swab (week 0)
  • current alcohol abuse
  • chronic heart disease
  • diabetes
  • current cigarette smoking

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 identifier (NCT number): NCT02012309

Contact: Lindsay K Nicholson, MD 303-399-8020 ext 3557
Contact: Edward N Janoff, MD 303-399-8020 ext 3258

United States, Colorado
University of Colorado-Denver Recruiting
Aurora, Colorado, United States, 80045
Denver Health and Hospitals Recruiting
Denver, Colorado, United States, 80204
Denver VA Medical Center Recruiting
Denver, Colorado, United States, 80220
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Edward N Janoff, MD University of Colorado-Denver, Denver VA Medical Center

Responsible Party: University of Colorado, Denver Identifier: NCT02012309     History of Changes
Other Study ID Numbers: 13-2405
R01AI108479 ( U.S. NIH Grant/Contract )
First Posted: December 16, 2013    Key Record Dates
Last Update Posted: January 18, 2018
Last Verified: January 2018

Keywords provided by University of Colorado, Denver:
Streptococcus pneumoniae infection
Streptococcus pneumoniae colonization
Pneumococcal vaccines
Nasopharyngeal microbiome

Additional relevant MeSH terms:
Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs