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Completed

NCT Number: NCT01916759

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

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Key information

Conditions

HIV Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Influenza Influenza, Human Lentivirus Infections Orthomyxoviridae Infections RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Kampala, Uganda

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • For HIV uninfected group
  • Confirmation of HIV-1 infection from medical records
  • 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
  • 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

  • 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)
  • 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
  • Received immunoglobulin or other blood product within the preceding 3 months or expected receipt of blood products during the 3 months of follow-up
  • 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)
  • History of severe reaction (including hypersensitivity) after receiving any vaccine
  • Currently pregnant
  • In the opinion of the study team it would be unsuitable for the study subjects to receive the vaccine or participate in the study.

Treatment and study plan

Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)

Drug

Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • Makerere University

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2013
Study completion
2014
First posted
Aug 6, 2013
Registry last updated
Apr 23, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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