Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.
Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, vario...
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Public Library of Science (PLoS)
2014-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0108383 |
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| author | Manjunatha M Venkataswamy Tony W Ng Shalu S Kharkwal Leandro J Carreño Alison J Johnson Shajo Kunnath-Velayudhan Zheng Liu Robert Bittman Peter J Jervis Liam R Cox Gurdyal S Besra Xiangshu Wen Weiming Yuan Moriya Tsuji Xiangming Li David D Ho John Chan Sunhee Lee Richard Frothingham Barton F Haynes Michael W Panas Geoffrey O Gillard Jaimie D Sixsmith Birgit Korioth-Schmitz Joern E Schmitz Michelle H Larsen William R Jacobs Steven A Porcelli |
| author_facet | Manjunatha M Venkataswamy Tony W Ng Shalu S Kharkwal Leandro J Carreño Alison J Johnson Shajo Kunnath-Velayudhan Zheng Liu Robert Bittman Peter J Jervis Liam R Cox Gurdyal S Besra Xiangshu Wen Weiming Yuan Moriya Tsuji Xiangming Li David D Ho John Chan Sunhee Lee Richard Frothingham Barton F Haynes Michael W Panas Geoffrey O Gillard Jaimie D Sixsmith Birgit Korioth-Schmitz Joern E Schmitz Michelle H Larsen William R Jacobs Steven A Porcelli |
| author_sort | Manjunatha M Venkataswamy |
| collection | DOAJ |
| description | Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors. |
| format | Article |
| id | doaj-art-90e45a31ded54c5cbca2c3231d0f0e54 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-90e45a31ded54c5cbca2c3231d0f0e542025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10838310.1371/journal.pone.0108383Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.Manjunatha M VenkataswamyTony W NgShalu S KharkwalLeandro J CarreñoAlison J JohnsonShajo Kunnath-VelayudhanZheng LiuRobert BittmanPeter J JervisLiam R CoxGurdyal S BesraXiangshu WenWeiming YuanMoriya TsujiXiangming LiDavid D HoJohn ChanSunhee LeeRichard FrothinghamBarton F HaynesMichael W PanasGeoffrey O GillardJaimie D SixsmithBirgit Korioth-SchmitzJoern E SchmitzMichelle H LarsenWilliam R JacobsSteven A PorcelliRecombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.https://doi.org/10.1371/journal.pone.0108383 |
| spellingShingle | Manjunatha M Venkataswamy Tony W Ng Shalu S Kharkwal Leandro J Carreño Alison J Johnson Shajo Kunnath-Velayudhan Zheng Liu Robert Bittman Peter J Jervis Liam R Cox Gurdyal S Besra Xiangshu Wen Weiming Yuan Moriya Tsuji Xiangming Li David D Ho John Chan Sunhee Lee Richard Frothingham Barton F Haynes Michael W Panas Geoffrey O Gillard Jaimie D Sixsmith Birgit Korioth-Schmitz Joern E Schmitz Michelle H Larsen William R Jacobs Steven A Porcelli Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. PLoS ONE |
| title | Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. |
| title_full | Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. |
| title_fullStr | Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. |
| title_full_unstemmed | Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. |
| title_short | Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. |
| title_sort | improving mycobacterium bovis bacillus calmette guerin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of nkt cells |
| url | https://doi.org/10.1371/journal.pone.0108383 |
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