Brief Title
Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults
Official Title
Immune Response to Pneumococcal Vaccination in Aging HIV Positive Individuals
Brief Summary
The investigators hypothesized that pneumococcal vaccination with either the 23-valent
pneumococcal polysaccharide vaccine PPV-23 (Pneumovax-23) alone or the 13-valent pneumococcal
conjugate vaccine PCV-13 (Prevnar-13) followed by PPV-23 results in a similar antibody
levels/functional antibody activity and induce similar pneumococcal polysaccharide
(PPS)-specific B cell response in HIV positive individuals > 50 years of age, HIV positive
individuals 21-40 years of age as compared to HIV negative > 50 years of age. The
investigators immunized the study groups HIV+ persons >50, HIV+ persons 21-40 and controls
(HIV negative) with PCV 13 followed by PPV23 and HIV>50 with PPV alone and examined immune
responses to polysaccharide (PPS) 23 (F),14, 3, 7 (F) and 19 (A) using polysaccharide
specific ELISA and opsonophagocytic assays (OPA). Pre- and post-immunization peripheral blood
samples were obtained. Extensive B cell phenotype analysis using fluorescent antibodies was
used to characterize PPS-labeled B cells. Specific phenotypes were correlated with antibody
levels and OPA and compared to populations immunized with PPV
Detailed Description
The purpose of this study is to learn more about how older people with HIV respond to the
pneumococcal or pneumonia vaccine. Pneumonia occurs very frequently in in older persons AND
in persons who are infected with HIV. Therefore, it is common practice to vaccinate against
pneumonia in these patient populations. Because older patients with HIV fit both of these
categories, it is believed that they are at an increased risk of pneumonia.
There are two types of pneumonia vaccines available for adults approved by the Federal Drug
Administration (FDA). One is called the pneumococcal polysaccharide vaccine (PPV23) and
protects against 23 different strains of the pneumonia bacteria. The other type of vaccine
called the pneumococcal conjugate vaccine (PCV13) protects against different strains of the
pneumonia bacteria.
Until 2012, it was recommended that all HIV-positive adults receive PPV23 when diagnosed with
HIV and again 5 years later. More recently, the guidelines have changed to all HIV-positive
adults are to receive PCV13, followed later with PPV23. At this point in time, it is not
clear which regimen works better in aging HIV positive adults. Investigators are doing this
study to compare the effectiveness of each vaccine regimen in aging HIV positive adults
compared to healthy adults. Although several studies show short-term efficacy or increased
antibody response in HIV+ persons with this vaccine, others do not, in either HIV+ population
or in elderly. Large efficacy trials necessary to establish clinical superiority of PCV
compared to PPV will likely not be conducted, particularly in the aging HIV+ population. It
is therefore essential to define immune responses to conjugated and free-polysaccharide
preparations by examining traditional antibody and functional levels as well as B cell
subsets, critically affected by aging and HIV. Will either PCV or PPV elicit an immune
response compatible with protection in this population? Based on persistent B cell
perturbations in HAART-treated persons, it is hypothesized that immunization of aging HIV+
persons with PPV23 will be as effective as a PCV13 containing regimen on a quantitative,
qualitative, B and T cell level and that the magnitude of this response will be related to
the degree of chronic inflammation. The proposed studies are highly significant as they will
define the B and T cell responses to a TI-2 and T-cell dependent form of pneumococcal vaccine
in the aging HIV+ population. These data will provide the necessary basis for development of
a rational vaccination approach, including the potential use of novel adjuvant. In this study
the investigators will:
1. Test the hypothesis that vaccination with either PPV alone (TI-2) or a PCV containing
regimen (TD) results in similar antibody levels/functional activity, that are determined
by levels of chronic inflammation in aging HIV+. The investigators will immunize the
study group HIV+ persons 50-65 and controls (HIV+21-40 and HIV- 50-65 years) with PCV13
followed by PPV23 and HIV+ 50-65 and HIV- 50-65 with PPV alone. The investigators will
examine immune responses to pneumococcal polysaccharides (PPS) 23 (F), 14, 3, 7 (F) and
19 (A) on a quantitative and qualitative level using ELISA and opsonophagocytic assays
(OPA) and correlate the response to the degree of inflammation measured in each
participant.
2. To test the hypothesis that the levels of antigen specific B cells identified with PPS
will be comparable between the PPV and PCV vaccine recipients. Pre- and
post-immunization peripheral blood samples will be obtained. Extensive phenotype
analysis using antibodies against cluster of differentiation (CD)19, 20, 21, 27, 38, 40,
immunoglobulin M (IgM) , B-cell activating factor (BAFF), trans-membrane activator and
calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation
antigen (BCMA) markers will be used to characterize PPS-labeled B cells. Specific
phenotypes will be correlated with antibody levels, OPA and inflammatory markers and
compared to the control populations immunized with PPV.
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Antibody response
Secondary Outcome
PPS-specific B cell phenotype
Condition
HIV Lipodystrophy
Intervention
Pneumococcal polysaccharide vaccine 23 valent
Study Arms / Comparison Groups
HIV+ 50-65, CD4>200 PCV/PPV
Description: HIV+ individuals , 50-65 years of age with a nadir cluster of differentiation (CD) 4 count >200 to receive PCV13 vaccine followed 8 weeks later by PPV23 Intervention: 13 valent Pneumococcal conjugate vaccine (PCV13) followed 8 weeks later by 23 valent pneumococcal polysaccharide vaccine
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
160
Start Date
September 1, 2015
Completion Date
March 30, 2020
Primary Completion Date
March 30, 2020
Eligibility Criteria
Inclusion Criteria:HIV+ 21-40 years of age HIV+ 50-65 years of age HIV- 50-65 years of age
-
Exclusion Criteria:
- Previous immunization with pneumococcal vaccine less than 5 years ago
- pregnancy and absence of contraceptive practice in women of childbearing age and
breast feeding
- known anaphylaxis, hypersensitivity to the pneumonia vaccine
- those who received blood products or gammaglobulin in last 3 months
- inability to comprehend or sihn informed consent
- Medications known to affect immune function (chemotherapy, an
angiotensin-converting-enzyme (ACE) inhibitors, corticosteroids, anti-TNFalpha agents)
- previous disease/present illness that may affect response to vaccination: previous
pneumococcal disease, removal of spleen, auto-immune disease, end stage renal disease
(ESRD) or end stage liver disease, cancer)
- significant (3x upper limit of normal) in complete blood count (CBC), chemistries,
immunoglobulin levels
Gender
All
Ages
21 Years - 65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Maria A. Julia Westerink, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03039491
Organization ID
MUSC vaccine study
Responsible Party
Sponsor
Study Sponsor
Medical University of South Carolina
Study Sponsor
Maria A. Julia Westerink, MD, Principal Investigator, Medical University of South Carolina
Verification Date
June 2020