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Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa

التفاصيل البيبلوغرافية
العنوان: Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa
المؤلفون: Sutherland, Jayne S, Lalor, Maeve K, Black, Gillian F, Ambrose, Lyn R, Loxton, Andre G, Chegou, Novel N, Kassa, Desta, Mihret, Adane, Howe, Rawleigh, Mayanja-Kizza, Harriet, Gomez, Marie P, Donkor, Simon, Franken, Kees, Hanekom, Willem, Klein, Michel R, Parida, Shreemanta K, Boom, W Henry, Thiel, Bonnie A, Crampin, Amelia C, Ota, Martin, Walzl, Gerhard, Ottenhoff, Tom H M, Dockrell, Hazel M, Kaufmann, Stefan H E
المصدر: GCGH Biomarkers for TB consortium , Sutherland , J S , Lalor , M K , Black , G F , Ambrose , L R , Loxton , A G , Chegou , N N , Kassa , D , Mihret , A , Howe , R , Mayanja-Kizza , H , Gomez , M P , Donkor , S , Franken , K , Hanekom , W , Klein , M R , Parida , S K , Boom , W H , Thiel , B A , Crampin , A C , Ota , M , Walzl ....
سنة النشر: 2013
المجموعة: University of Groningen research database
مصطلحات موضوعية: Adult, Africa South of the Sahara/epidemiology, Antigens, Bacterial/immunology, CD4 Lymphocyte Count, Cluster Analysis, Coinfection, Female, HIV Infections/epidemiology, Humans, Interferon-gamma/blood, Male, Middle Aged, Mycobacterium tuberculosis/immunology, Tuberculosis/epidemiology, Young Adult
الوصف: BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: https://research.rug.nl/en/publications/9a0c1adc-a7ee-447b-a08a-a0f4026ab458Test
DOI: 10.1371/journal.pone.0074080
الإتاحة: https://doi.org/10.1371/journal.pone.0074080Test
https://hdl.handle.net/11370/9a0c1adc-a7ee-447b-a08a-a0f4026ab458Test
https://research.rug.nl/en/publications/9a0c1adc-a7ee-447b-a08a-a0f4026ab458Test
https://pure.rug.nl/ws/files/168475716/pone.0074080.pdfTest
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.42C06998
قاعدة البيانات: BASE
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