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

NCT02012309 | Unknown DMC

• 2 other identifiers: 13-2405R01AI108479
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Human Immunodeficiency Virus (HIV) infection is complicated by high rates of infections and cancers which are often the cause of death rather than the HIV/acquired immune deficiency syndrome (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.

Conditions

HIV; Pneumococcal Infections; Pneumococcal Vaccines

Keywords

HIV; Streptococcus pneumoniae infection; Streptococcus pneumoniae colonization; Pneumococcal vaccines; Prevnar; Pneumovax; Nasopharyngeal microbiome

Outcome Measures

Primary Outcomes (4)

• B and T cell subsets

  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

  Weeks -12, 0, 1, 8, 9, 16

• Total IgG, IgM and IgA

  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)

  Weeks -12, 0, 1, 8, 9, 16

• Antibody-secreting cells

  Total IgG, IgM and IgA antibody-secreting cells (ASC) enumerated by enzyme-linked immunospot (ELISPOT) on day 0 and day 7

  Weeks 0, 1, 8, 9

• AID and BCL-6 production

  RNA extraction for activation-induced cytidine deaminase (AID) and B cell lymphoma protein 6 (BCL6) expression and mutation from stimulated B cells

  Weeks -12, 0, 1, 8, 9, 16

Secondary Outcomes (2)

• S.pneumoniae colonization and nasopharyngeal microbiome

  Weeks -12, 0, 8, 16

• S.pneumoniae urine antigen positivity

  Week -12

Study Arms (2)

HIV-seronegative

EXPERIMENTAL

HIV-seronegative subjects will receive Prevnar (PCV-13) at week 0.

Biological: PCV-13

HIV-infected

EXPERIMENTAL

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; Biological: PPSV-23

Interventions

PCV-13 BIOLOGICAL

Also known as: Prevnar

HIV-infected; HIV-seronegative

PPSV-23 BIOLOGICAL

Also known as: Pneumovax

HIV-infected

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (3)

University of Colorado-Denver

Aurora, Colorado, 80045, United States

Location

Denver Health and Hospitals

Denver, Colorado, 80204, United States

Location

Denver VA Medical Center

Denver, Colorado, 80220, United States

Location

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine; Heptavalent Pneumococcal Conjugate Vaccine; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined

Study Officials

• Edward N Janoff, MD

  University of Colorado-Denver, Denver VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 16, 2013
• Study Start: August 1, 2014
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: November 18, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)