Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response

Christof Geldmacher, Ian S. Metzler, Sodsai Tovanabutra, Tedi E. Asher, Emma Gostick, David R. Ambrozak, Constantinos Petrovas, Alexandra Schuetz, Njabulo Ngwenyama, Gustavo Kijak, Leonard Maboko, Michael Hoelscher, Francine McCutchan, David A. Price, Daniel C. Douek, Richard A. Koup

Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting.......

Published at:  2009-08-20

Contraceptive Use in Women Enrolled into Preventive HIV Vaccine Trials: Experience from a Phase I/II Trial in East Africa

Hannah Kibuuka ,David Guwatudde,Robert Kimutai,Lucas Maganga,Leonard Maboko,Cecilia Watyema,Fredrick Sawe,Douglas Shaffer,Dickson Matsiko,Monica Millard,Nelson Michael,Fred Wabwire-Mangen,Merlin Robb

HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial.

Published at:  2009-04-10

Early Depletion of Mycobacterium tuberculosis-Specific T Helper 1 Cell Responses after HIV-1 Infection

Christof Geldmacher, Alexandra Schuetz, Njabulo Ngwenyama, Joseph P. Casazza, Erica Sanga, Elmar Saathoff, Catharina Boehme, Steffen Geis, Leonard Maboko, Mahavir Singh, Fred Minja, Andreas Meyerhans, Richard A. Koup, Michael Hoelscher

The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis-specific pathogenicity early after onset of HIV infection

Published at:  2008-12-01

Laboratory reference values for healthy adults from southern Tanzania

Elmar Saathoff, Philine Schneider, Vera Kleinfeldt, Steffen Geis, Dennis Haule, Leonard Maboko, Eleuter Samky, Mark de Souza, Merlin Robb, Michael Hoelscher

Clinical laboratory reference ranges are an important tool for identifying abnormal laboratory results and for ultimately guiding patient management decisions. Because measured laboratory parameters are influenced not only by individual factors such as age, sex, lifestyle, etc. but also by population and ecological factors such as ethnic background, climate and altitude, they vary not only between individuals but also between populations

Published at:  2008-04-16

Peptide Impurities in Commercial Synthetic Peptides and Their Implications for Vaccine Trial Assessment

Authors: Jeffrey R. Currier, Lynee M. Galley, Holger Wenschuh, Vivian Morafo, Silvia Ratto-Kim, Clive M. Gray, Leonard Maboko, Michael Hoelscher, Mary A. Marovich, Josephine H. Cox

The advent of T-cell assay methodologies that are amenable to high throughput coupled with the availability of large libraries of overlapping peptides have revolutionized the fields of vaccine efficacy testing and cellular immune response assessment. Since T-cell assay performance is critically dependent upon the quality and specificity of the stimulating peptides, assurance of high-quality and reliable input peptides is an important aspect of assay validation. Herein, we demonstrate that individual peptides from large human immunodeficiency virus.........

Published at:  2008-02-01

CD8 T-Cell Recognition of Multiple Epitopes within Specific Gag Regions Is Associated with Maintenance of a Low Steady-State Viremia in Human Immunodeficiency Virus Type 1-Seropositive Patients

Authors: Christof Geldmacher, Jeffrey R. Currier, Eva Herrmann, Antelmo Haule, Ellen Kuta, Francine McCutchan, Lilian Njovu, Steffen Geis, Oliver Hoffmann, Leonard Maboko, Carolyn Williamson, Deborah Birx, Andreas Meyerhans, Josephine Cox, Michael Hoelscher

The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell.....

Published at:  2007-03-01

Molecular surveillance of drug-resistance associated mutations of Plasmodium falciparum in south-west Tanzania

Mirjam Schönfeld, Isabel Barreto Miranda, Mirjam Schunk, Ibrahim Maduhu, Leonard Maboko, Michael Hoelscher, Nicole Berens-Riha, Andrew Kitua & Thomas Löscher

In Tanzania, drug-resistant malaria parasites are an increasing public health concern. Because of widespread chloroquine (CQ) resistance Tanzania changed its first line treatment recommendations for uncomplicated malaria from CQ to sulfadoxine-pyrimethamine (SP) in 2001. Loss of SP sensitivity is progressing rapidly. SP resistance is associated with mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes.

Published at:  2007-01-15

In a mixed subtype epidemic, the HIV-1 Gag-specific T-cell response is biased towards the infecting subtype

Geldmacher, Christofa,b; Currier, Jeffrey Rc; Gerhardt, Martinab; Haule, Antelmoa; Maboko, Leonarda; Birx, Deborahc; Gray, Clived; Meyerhans, Andrease; Cox, Josephinec; Hoelscher, Michaelb

Southwest Tanzania is affected by an HIV-1 epidemic consisting of subtypes A, C, and D, and their recombinant forms. This study was designed to assess whether the Gag- and Nef-specific T-cell response is biased towards recognizing the infecting subtype.

Published at:  2007-01-11

Frequency of HIV Type 1 Dual Infection and HIV Diversity: Analysis of Low- and High-Risk Populations in Mbeya Region, Tanzania

Karl-Heinz Herbinger, Martina Gerhardt, Sucheep Piyasirisilp, Doreen Mloka, Miguel A. Arroyo, Oliver Hoffmann, Leonard Maboko, Deborah L. Birx, Donan Mmbando, Francine E. Mccutchan, and Michael Hoelscher

HIV-1 diversity, frequency of recombinants, and dual infection were determined in two populations with different HIV risk behavior. A high-risk cohort of 600 female bar workers and a normal-risk population of 1108 antenatal clinic attendees and blood donors were recruited. Behavioral data were assessed and blood for HIV- 1 diagnosis and genotyping was sampled. HIV-1 subtypes were defined through the multiregion hybridization assay (MHAacd). HIV-1 prevalence differed significantly among the two populations. The prevalence was 67.8% in the population of bar workers and 17% in the normal-risk population (antenatal care attendees and blood donors). Within the normal-risk population the HIV-1 prevalence was lowest in the group of volunteer blood donors. The frequency of HIV-1 infection in women was 1.7 times.......

Published at:  2006-07-10

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