Improving Mycobacterium bovis bacillus calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells

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 & 8 others Michael W. Panas, Geoffrey O. Gillard, Jaimie D. Sixsmith, Birgit Korioth-Schmitz, Joern E. Schmitz, Michelle H. Larsen, William R. Jacobs, Steven A. Porcelli

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere108383
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 25 2014
Externally publishedYes

Fingerprint

Natural Killer T-Cells
T-cells
Viral Antigens
viral antigens
Mycobacterium bovis
glycolipids
Glycolipids
natural killer cells
Bacilli
Bacillus
Vaccines
T-lymphocytes
vaccines
T-Lymphocytes
AIDS Vaccines
antigens
Primates
adjuvants
CD1d Antigen
immune response

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Venkataswamy, M. M., Ng, T. W., Kharkwal, S. S., Carreño, L. J., Johnson, A. J., Kunnath-Velayudhan, S., ... Porcelli, S. A. (2014). Improving Mycobacterium bovis bacillus calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. PloS one, 9(9), [e108383]. https://doi.org/10.1371/journal.pone.0108383

Improving Mycobacterium bovis bacillus calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. / Venkataswamy, Manjunatha M.; Ng, Tony W.; Kharkwal, Shalu S.; Carreño, Leandro J.; Johnson, Alison J.; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J.; Cox, Liam R.; Besra, Gurdyal S.; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D.; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F.; Panas, Michael W.; Gillard, Geoffrey O.; Sixsmith, Jaimie D.; Korioth-Schmitz, Birgit; Schmitz, Joern E.; Larsen, Michelle H.; Jacobs, William R.; Porcelli, Steven A.

In: PloS one, Vol. 9, No. 9, e108383, 25.09.2014.

Research output: Contribution to journalArticle

Venkataswamy, MM, Ng, TW, Kharkwal, SS, Carreño, LJ, Johnson, AJ, Kunnath-Velayudhan, S, Liu, Z, Bittman, R, Jervis, PJ, Cox, LR, Besra, GS, Wen, X, Yuan, W, Tsuji, M, Li, X, Ho, DD, Chan, J, Lee, S, Frothingham, R, Haynes, BF, Panas, MW, Gillard, GO, Sixsmith, JD, Korioth-Schmitz, B, Schmitz, JE, Larsen, MH, Jacobs, WR & Porcelli, SA 2014, 'Improving Mycobacterium bovis bacillus calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells', PloS one, vol. 9, no. 9, e108383. https://doi.org/10.1371/journal.pone.0108383
Venkataswamy, Manjunatha M. ; Ng, Tony W. ; Kharkwal, Shalu S. ; Carreño, Leandro J. ; Johnson, Alison J. ; Kunnath-Velayudhan, Shajo ; Liu, Zheng ; Bittman, Robert ; Jervis, Peter J. ; Cox, Liam R. ; Besra, Gurdyal S. ; Wen, Xiangshu ; Yuan, Weiming ; Tsuji, Moriya ; Li, Xiangming ; Ho, David D. ; Chan, John ; Lee, Sunhee ; Frothingham, Richard ; Haynes, Barton F. ; Panas, Michael W. ; Gillard, Geoffrey O. ; Sixsmith, Jaimie D. ; Korioth-Schmitz, Birgit ; Schmitz, Joern E. ; Larsen, Michelle H. ; Jacobs, William R. ; Porcelli, Steven A. / Improving Mycobacterium bovis bacillus calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells. In: PloS one. 2014 ; Vol. 9, No. 9.
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