Differences in Response to the Flu Vaccine Among Adults With HIV and Without HIV in Uganda
22 de abril de 2014 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
63
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Kampala, Uganda
- Makere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Otro: 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®).
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Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.
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Otro: 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®).
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Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.
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Otro: 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®).
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Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)
Periodo de tiempo: From baseline (Day 0) to 100 days post vaccination
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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.
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From baseline (Day 0) to 100 days post vaccination
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Proportion of subjects achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases.
Periodo de tiempo: From baseline (Day 0) to 100 days following primary vaccination
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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.
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From baseline (Day 0) to 100 days following primary vaccination
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Calculating correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza.
Periodo de tiempo: From baseline (Day 0) to 100 days post vaccination
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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.
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From baseline (Day 0) to 100 days post vaccination
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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
Periodo de tiempo: From baseline (Day 0) to Day 28 post vaccination
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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
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From baseline (Day 0) to Day 28 post vaccination
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Correlation between microbiata status and the quality of immune response elicited in vaccinated individuals
Periodo de tiempo: From baseline (Day 0) to Day 28 post vaccination
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Determine whether the status of the microbita correlates with the quality of immune responses elicited in vaccinated individuals
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From baseline (Day 0) to Day 28 post vaccination
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Saad B Omer, MBBS,MPH,PhD, Emory Unversity
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Malaspina A, Moir S, Orsega SM, Vasquez J, Miller NJ, Donoghue ET, Kottilil S, Gezmu M, Follmann D, Vodeiko GM, Levandowski RA, Mican JM, Fauci AS. Compromised B cell responses to influenza vaccination in HIV-infected individuals. J Infect Dis. 2005 May 1;191(9):1442-50. doi: 10.1086/429298. Epub 2005 Mar 24.
- Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067.
- Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio RZ, Mulligan M, Aderem A, Ahmed R, Pulendran B. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009 Jan;10(1):116-125. doi: 10.1038/ni.1688. Epub 2008 Nov 23.
- 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.
- Tebas P, Frank I, Lewis M, Quinn J, Zifchak L, Thomas A, Kenney T, Kappes R, Wagner W, Maffei K, Sullivan K; Center for AIDS Research and Clinical Trials Unit of the University of Pennsylvania. Poor immunogenicity of the H1N1 2009 vaccine in well controlled HIV-infected individuals. AIDS. 2010 Sep 10;24(14):2187-92. doi: 10.1097/QAD.0b013e32833c6d5c.
- Beck JM, Rosen MJ, Peavy HH. Pulmonary complications of HIV infection. Report of the Fourth NHLBI Workshop. Am J Respir Crit Care Med. 2001 Dec 1;164(11):2120-6. doi: 10.1164/ajrccm.164.11.2102047. No abstract available.
- 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.
- 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.
- 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.
- 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. Erratum In: J Exp Med. 2011 Feb 14;208(2):411.
- 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. Erratum In: Immunity. 2011 Jan 28;34(1):135.
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de junio de 2013
Finalización primaria (Actual)
1 de diciembre de 2013
Finalización del estudio (Actual)
1 de marzo de 2014
Fechas de registro del estudio
Enviado por primera vez
25 de febrero de 2013
Primero enviado que cumplió con los criterios de control de calidad
4 de agosto de 2013
Publicado por primera vez (Estimar)
6 de agosto de 2013
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
23 de abril de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
22 de abril de 2014
Última verificación
1 de abril de 2014
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones por virus de ARN
- Enfermedades virales
- Infecciones
- Infecciones del Tracto Respiratorio
- Enfermedades de las vías respiratorias
- Infecciones transmitidas por la sangre
- Enfermedades contagiosas
- Enfermedades De Transmisión Sexual Virales
- Enfermedades de transmisión sexual
- Infecciones por lentivirus
- Infecciones por retroviridae
- Enfermedades del sistema inmunológico
- Infecciones por Orthomyxoviridae
- Enfermedades de virus lentos
- Infecciones por VIH
- Influenza Humana
- Síndrome de inmunodeficiencia adquirida
- Síndromes de deficiencia inmunológica
Otros números de identificación del estudio
- IRB00058919
- 1U19AI090023-02 (Subvención/contrato del NIH de EE. UU.)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .