Differences in Response to the Flu Vaccine Among Adults With HIV and Without HIV in Uganda

April 22, 2014 updated by: Saad B. Omer, PhD, Emory University

Systems Biological Responses to Influenza Vaccination in an HIV-infected and HIV-uninfected Adult Population in Kampala, Uganda

To use a systems biological approach to study the molecular signatures of innate and adaptive responses to vaccination in a HIV infected versus uninfected adult population in Kampala, Uganda.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This longitudinal, observational cohort study will be conducted at the Makerere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital complex in Kampala Uganda. The study will consist of 2 groups. One group will consist of 25 healthy HIV uninfected adults and the other arm will consist of 35 HIV infected adults. Within the HIV infected arm there will be two groups, 25 HIV infected adults and 10 long term non-progressors. Vaccinees will receive a primary immunization at day 0, and blood samples will be obtained at days 0, 1, 3, 7, 14, 28 and 100 after immunization.

We will analyze the early molecular signatures (identified by microarray analyses, as well as by FACS analyses of innate immune cells and luminex analyses of cytokines and chemokines) that correlate and predict the later immune responses.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Kampala, Uganda
        • Makere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. For HIV uninfected group

    • Confirmation of HIV-1 infection from medical records

  2. For HIV infected on HAART group

    • Confirmation of HIV-1 infection from medical records
    • Participants must be on HAART for at least 6 months prior to enrollment
    • A CD4 T-cell count available in the last 6 months
    • CD4 T-cell count >350 cells/μL on the eligibility blood specimen

  3. Long-term non-progressor group

    • HIV infected for more than 7 years
    • No evidence of opportunistic infections in the medical records
    • Never received antiretroviral therapy (except anti-retrovirals for prevention of mother-to-infant transmission of HIV)
    • A CD4 T-cell count available in the last 6 months
    • CD4+ T-cell count slop of ≥0 cells/µl blood from entry into the MU-JHU cohort until the most recent available CD4+ T-cell count.

Exclusion Criteria:

  1. Current moderate or severe acute illness, history of fever or temperature ≥37.5oC within 48 hours prior to vaccination (participants can be re-evaluated at a subsequent visit)
  2. History of systemic disease, including: Guillain-Barré Syndrome; known hepatitis B, or hepatitis C infection; cardiac disease; uncontrolled diabetes mellitus (including gestational diabetes); chronic liver condition; clinically significant renal impairment; clinically significant neurological disorders; active TB within the last year; Cancer. This information will be based on self-reporting and (where possible) will be confirmed by hospital medical records
  3. Received immunoglobulin or other blood product within the preceding 3 months or expected receipt of blood products during the 3 months of follow-up
  4. History of anaphylactic hypersensitivity reactions to egg proteins (eggs or egg products), or any other component of the vaccine including traces (formaldehyde, octoxinol 9 (Triton X-100) and neomycin)
  5. History of severe reaction (including hypersensitivity) after receiving any vaccine
  6. Currently pregnant
  7. In the opinion of the study team it would be unsuitable for the study subjects to receive the vaccine or participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: HIV uninfected adults
25 HIV uninfected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).
Drug: Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)
Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.
Other: HIV infected adults on HAART
25 HIV infected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).
Drug: Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)
Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.
Other: HIV-infected long-term non-progressors
10 HIV-infected long-term non-progressor adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).
Drug: Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)
Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)
Time Frame: From baseline (Day 0) to 100 days post vaccination
Immune parameters or gene expressions that change significantly in groups over baseline post immunization and between the study groups will be analyzed. For immune parameters, we will use a two-sided paired t-test. Fold-change will be combined with the test p-value in a selection criterion as appropriate. The tentative selection criterion is p-value ≤ 0.01 and fold change ≥ 3. For the gene/miRNA expression data, we will use the method Significance Analysis of Microarrays (SAM) with paired design to find differentially expressed genes. False discovery rate (FDR) will be used as selection criterion. The tentative selection criterion is FDR ≤ 0.1.
From baseline (Day 0) to 100 days post vaccination
Proportion of subjects achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases.
Time Frame: From baseline (Day 0) to 100 days following primary vaccination
Proportion of subjects in different study groups achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases will be tabulated at each time point (Days 0, 1, 3, 7, 14, 28 and 100) and plotted across time. Fisher's exact test will be used to make comparisons between the study groups.
From baseline (Day 0) to 100 days following primary vaccination
Calculating correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza.
Time Frame: From baseline (Day 0) to 100 days post vaccination
For immune parameters, we will calculate the correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza. The p-values associated with the correlation coefficients will be used to select immune parameters that are associated with the respective adaptive immune responses. The tentative selection criterion is p-value ≤ 0.01. For gene expression data, we will use the method Significance Analysis of Microarrays (SAM) with quantitative outcome to identify genes that are significantly associated with the immune response. False discovery rate (FDR) will be used as selection criterion. The tentative selection criterion is FDR ≤ 0.1.
From baseline (Day 0) to 100 days post vaccination
Characterization of the gut microbiota to determine compositional differences between HIV-uninfected adults versus HIV-infected adults on HAART versus HIV-infected long-term non-progressors
Time Frame: From baseline (Day 0) to Day 28 post vaccination
Gut mircobiota will be characterized to determine what compositional differences exist between HIV-uninfected adults versus HIV-infected adults on HAARt versus HIV-infected long-term non-progressors at baseline (Day 0), Day 7 and Day 28 post vaccination
From baseline (Day 0) to Day 28 post vaccination
Correlation between microbiata status and the quality of immune response elicited in vaccinated individuals
Time Frame: From baseline (Day 0) to Day 28 post vaccination
Determine whether the status of the microbita correlates with the quality of immune responses elicited in vaccinated individuals
From baseline (Day 0) to Day 28 post vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

Makerere University

Investigators

  • Principal Investigator: Saad B Omer, MBBS,MPH,PhD, Emory Unversity

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

February 25, 2013

First Submitted That Met QC Criteria

August 4, 2013

First Posted (Estimate)

August 6, 2013

Study Record Updates

Last Update Posted (Estimate)

April 23, 2014

Last Update Submitted That Met QC Criteria

April 22, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00058919
  • 1U19AI090023-02 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acquired Immunodeficiency Syndrome

Clinical Trials on Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe