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

NCT01916759 | Completed

• 2 other identifiers: IRB000589191U19AI090023-02
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV; Acquired Immunodeficiency Syndrome; Influenza

Keywords

immunization

Outcome Measures

Primary Outcomes (5)

• In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)

  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.

  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.

  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

  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

  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

Study Arms (3)

HIV uninfected adults

OTHER

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®)

HIV infected adults on HAART

OTHER

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®)

HIV-infected long-term non-progressors

OTHER

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®)

Interventions

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.

HIV infected adults on HAART; HIV uninfected adults; HIV-infected long-term non-progressors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Makerere University: collaborator

Study Sites (1)

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

Kampala, Uganda

Location

Related Publications (12)

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  PMID: 15809902 BACKGROUND

• Zanetti AR, Amendola A, Besana S, Boschini A, Tanzi E. Safety and immunogenicity of influenza vaccination in individuals infected with HIV. Vaccine. 2002 Dec 20;20 Suppl 5:B29-32. doi: 10.1016/s0264-410x(02)00511-x.

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• Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, Basser RL. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med. 2009 Dec 17;361(25):2405-13. doi: 10.1056/NEJMoa0907413. Epub 2009 Sep 10.

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• Pallikkuth S, Kanthikeel SP, Silva SY, Fischl M, Pahwa R, Pahwa S. Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients. J Allergy Clin Immunol. 2011 Dec;128(6):1279-85. doi: 10.1016/j.jaci.2011.05.033. Epub 2011 Jul 12.

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• Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, James J, Air GM, Capra JD, Ahmed R, Wilson PC. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008 May 29;453(7195):667-71. doi: 10.1038/nature06890. Epub 2008 Apr 30.

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• Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O'Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med. 2011 Jan 17;208(1):181-93. doi: 10.1084/jem.20101352. Epub 2011 Jan 10.

  PMID: 21220454 BACKGROUND

• Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity. 2011 Jan 28;34(1):108-21. doi: 10.1016/j.immuni.2010.12.012. Epub 2011 Jan 6.

  PMID: 21215658 BACKGROUND

• DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004, Clarification August 2009. Available at rcc.tech-res-intl.com.

  BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Influenza, Human

Interventions

vaxigrip

Condition Hierarchy (Ancestors)

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

Study Officials

• Saad B Omer, MBBS,MPH,PhD

  Emory Unversity

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: August 6, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

UG (1)