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.
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 area...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3769366?pdf=render |
| _version_ | 1818230862477524992 |
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| author | Jayne S Sutherland Maeve K Lalor Gillian F Black Lyn R Ambrose Andre G Loxton Novel N Chegou Desta Kassa Adane Mihret Rawleigh Howe Harriet Mayanja-Kizza Marie P Gomez Simon Donkor Kees Franken Willem Hanekom Michel R Klein Shreemanta K Parida W Henry Boom Bonnie A Thiel Amelia C Crampin Martin Ota Gerhard Walzl Tom H M Ottenhoff Hazel M Dockrell Stefan H E Kaufmann GCGH Biomarkers for TB consortium |
| author_facet | Jayne S Sutherland Maeve K Lalor Gillian F Black Lyn R Ambrose Andre G Loxton Novel N Chegou Desta Kassa Adane Mihret Rawleigh Howe Harriet Mayanja-Kizza Marie P Gomez Simon Donkor Kees Franken Willem Hanekom Michel R Klein Shreemanta K Parida W Henry Boom Bonnie A Thiel Amelia C Crampin Martin Ota Gerhard Walzl Tom H M Ottenhoff Hazel M Dockrell Stefan H E Kaufmann GCGH Biomarkers for TB consortium |
| author_sort | Jayne S Sutherland |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T10:41:14Z |
| format | Article |
| id | doaj.art-123f1077ef0d46748fd6f8db23b29b37 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T10:41:14Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-123f1077ef0d46748fd6f8db23b29b372022-12-22T00:27:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7408010.1371/journal.pone.0074080Analysis 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.Jayne S SutherlandMaeve K LalorGillian F BlackLyn R AmbroseAndre G LoxtonNovel N ChegouDesta KassaAdane MihretRawleigh HoweHarriet Mayanja-KizzaMarie P GomezSimon DonkorKees FrankenWillem HanekomMichel R KleinShreemanta K ParidaW Henry BoomBonnie A ThielAmelia C CrampinMartin OtaGerhard WalzlTom H M OttenhoffHazel M DockrellStefan H E KaufmannGCGH Biomarkers for TB consortiumBACKGROUND: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.http://europepmc.org/articles/PMC3769366?pdf=render |
| spellingShingle | Jayne S Sutherland Maeve K Lalor Gillian F Black Lyn R Ambrose Andre G Loxton Novel N Chegou Desta Kassa Adane Mihret Rawleigh Howe Harriet Mayanja-Kizza Marie P Gomez Simon Donkor Kees Franken Willem Hanekom Michel R Klein Shreemanta K Parida W Henry Boom Bonnie A Thiel Amelia C Crampin Martin Ota Gerhard Walzl Tom H M Ottenhoff Hazel M Dockrell Stefan H E Kaufmann GCGH Biomarkers for TB consortium 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | http://europepmc.org/articles/PMC3769366?pdf=render |
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