HIV, Pneumococcal Infections, Pneumococcal Vaccines
Conditions
Keywords
HIV, Streptococcus pneumoniae infection, Streptococcus pneumoniae colonization, Pneumococcal vaccines, Prevnar, Pneumovax, Nasopharyngeal microbiome
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.
Interventions
BIOLOGICALPCV-13
BIOLOGICALPPSV-23
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| B and T cell subsets | 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 |
| Total IgG, IgM and IgA | 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) |
| Antibody-secreting cells | 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 |
| AID and BCL-6 production | 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
| Measure | Time frame | Description |
|---|---|---|
| S.pneumoniae colonization and nasopharyngeal microbiome | 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 |
| S.pneumoniae urine antigen positivity | Week -12 | S. pneumoniae urine antigen positivity in relation to colonization |
Countries
United States
Outcome results
None listed