Back to results

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

Primary Purpose

HIV, Pneumococcal Infections, Pneumococcal Vaccines

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

PCV-13

PPSV-23

About this trial

This is an interventional prevention trial for HIV focused on measuring HIV, Streptococcus pneumoniae infection, Streptococcus pneumoniae colonization, Pneumococcal vaccines, Prevnar, Pneumovax, Nasopharyngeal microbiome

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Colorado-Denver
Denver Health and Hospitals
Denver VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

HIV-seronegative

HIV-infected

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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

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)

Antibody-secreting cells

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

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

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

S.pneumoniae urine antigen positivity

S. pneumoniae urine antigen positivity in relation to colonization

Full Information

NCT ID

NCT02012309

First Posted

December 10, 2013

Last Updated

November 17, 2020

Sponsor

University of Colorado, Denver

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT02012309

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 2014 (Actual)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, Pneumococcal Infections, Pneumococcal Vaccines

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HIV-seronegative

Arm Type

Experimental

Arm Description

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

Arm Title

HIV-infected

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

PCV-13

Other Intervention Name(s)

Prevnar

Intervention Type

Biological

Intervention Name(s)

PPSV-23

Other Intervention Name(s)

Pneumovax

Primary Outcome Measure Information:

Title

B and T cell subsets

Description

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

Time Frame

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

Title

Total IgG, IgM and IgA

Description

Time Frame

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

Title

Antibody-secreting cells

Description

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

Time Frame

Weeks 0, 1, 8, 9

Title

AID and BCL-6 production

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

S.pneumoniae colonization and nasopharyngeal microbiome

Description

Time Frame

Weeks -12, 0, 8, 16

Title

S.pneumoniae urine antigen positivity

Description

S. pneumoniae urine antigen positivity in relation to colonization

Time Frame

Week -12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward N Janoff, MD

Organizational Affiliation

University of Colorado-Denver, Denver VA Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado-Denver

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Denver Health and Hospitals

City

Denver

State/Province

Colorado

ZIP/Postal Code

80204

Country

United States

Facility Name

Denver VA Medical Center

City

Denver

State/Province

Colorado

ZIP/Postal Code

80220

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs