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

HIV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02012309
• Other study ID #: 13-2405
• Secondary ID: R01AI108479
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 2014
• Est. completion date: June 2021

Study information

• Verified date: November 2020
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: June 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV
• Pneumococcal Infections
• Pneumococcal Vaccines

Intervention

Biological:
• PCV-13

• PPSV-23

Locations

Country	Name	City	State
United States	University of Colorado-Denver	Aurora	Colorado
United States	Denver Health and Hospitals	Denver	Colorado
United States	Denver VA Medical Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	S.pneumoniae colonization and nasopharyngeal microbiome	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	Weeks -12, 0, 8, 16
Secondary	S.pneumoniae urine antigen positivity	S. pneumoniae urine antigen positivity in relation to colonization	Week -12