Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine

Regan J. Anderson, Jasmine Li, Lukasz Kedzierski, Benjamin J. Compton, Colin M. Hayman, Taryn L. Osmond, Ching Wen Tang, Kathryn J. Farrand, Hui Fern Koay, Catarina Filipa Dos Santos Sa E. Almeida, Lauren R. Holz, Geoffrey M. Williams, Margaret A. Brimble, Zhongfang Wang, Marios Koutsakos, Katherine Kedzierska, Dale I. Godfrey, Ian F. Hermans, Stephen J. Turner, Gavin F. Painter

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing health goal, particularly in the context of the increasing threat of new global pandemics. Vaccines that specifically induce T cell responses are of considerable interest because they can target viral proteins that are more likely to be shared between different virus strains and subtypes and hence provide effective cross-reactive IAV immunity. From a practical perspective, such vaccines should induce T cell responses with long-lasting memory, while also being simple to manufacture and cost-effective. Here we describe the synthesis and evaluation of a vaccine platform based on solid phase peptide synthesis and bio-orthogonal conjugation methodologies. The chemical approach involves covalently attaching synthetic long peptides from a virus-associated protein to a powerful adjuvant molecule, α-galactosylceramide (α-GalCer). Strain-promoted azide-alkyne cycloaddition is used as a simple and efficient method for conjugation, and pseudoproline methodology is used to increase the efficiency of the peptide synthesis. α-GalCer is a glycolipid that stimulates NKT cells, a population of lymphoid-resident immune cells that can provide potent stimulatory signals to antigen-presenting cells engaged in driving proliferation and differentiation of peptide-specific T cells. When used in mice, the vaccine induced T cell responses that provided effective prophylactic protection against IAV infection, with the speed of viral clearance greater than that seen from previous viral exposure. These findings are significant because the vaccines are highly defined, quick to synthesize, and easily characterized and are therefore appropriate for large scale affordable manufacture.

Original languageEnglish
Pages (from-to)2898-2905
Number of pages8
JournalACS Chemical Biology
Volume12
Issue number11
DOIs
Publication statusPublished - 17 Nov 2017

Cite this

Anderson, R. J., Li, J., Kedzierski, L., Compton, B. J., Hayman, C. M., Osmond, T. L., ... Painter, G. F. (2017). Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine. ACS Chemical Biology, 12(11), 2898-2905. https://doi.org/10.1021/acschembio.7b00845
Anderson, Regan J. ; Li, Jasmine ; Kedzierski, Lukasz ; Compton, Benjamin J. ; Hayman, Colin M. ; Osmond, Taryn L. ; Tang, Ching Wen ; Farrand, Kathryn J. ; Koay, Hui Fern ; Almeida, Catarina Filipa Dos Santos Sa E. ; Holz, Lauren R. ; Williams, Geoffrey M. ; Brimble, Margaret A. ; Wang, Zhongfang ; Koutsakos, Marios ; Kedzierska, Katherine ; Godfrey, Dale I. ; Hermans, Ian F. ; Turner, Stephen J. ; Painter, Gavin F. / Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine. In: ACS Chemical Biology. 2017 ; Vol. 12, No. 11. pp. 2898-2905.
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abstract = "The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing health goal, particularly in the context of the increasing threat of new global pandemics. Vaccines that specifically induce T cell responses are of considerable interest because they can target viral proteins that are more likely to be shared between different virus strains and subtypes and hence provide effective cross-reactive IAV immunity. From a practical perspective, such vaccines should induce T cell responses with long-lasting memory, while also being simple to manufacture and cost-effective. Here we describe the synthesis and evaluation of a vaccine platform based on solid phase peptide synthesis and bio-orthogonal conjugation methodologies. The chemical approach involves covalently attaching synthetic long peptides from a virus-associated protein to a powerful adjuvant molecule, α-galactosylceramide (α-GalCer). Strain-promoted azide-alkyne cycloaddition is used as a simple and efficient method for conjugation, and pseudoproline methodology is used to increase the efficiency of the peptide synthesis. α-GalCer is a glycolipid that stimulates NKT cells, a population of lymphoid-resident immune cells that can provide potent stimulatory signals to antigen-presenting cells engaged in driving proliferation and differentiation of peptide-specific T cells. When used in mice, the vaccine induced T cell responses that provided effective prophylactic protection against IAV infection, with the speed of viral clearance greater than that seen from previous viral exposure. These findings are significant because the vaccines are highly defined, quick to synthesize, and easily characterized and are therefore appropriate for large scale affordable manufacture.",
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Anderson, RJ, Li, J, Kedzierski, L, Compton, BJ, Hayman, CM, Osmond, TL, Tang, CW, Farrand, KJ, Koay, HF, Almeida, CFDSSE, Holz, LR, Williams, GM, Brimble, MA, Wang, Z, Koutsakos, M, Kedzierska, K, Godfrey, DI, Hermans, IF, Turner, SJ & Painter, GF 2017, 'Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine' ACS Chemical Biology, vol. 12, no. 11, pp. 2898-2905. https://doi.org/10.1021/acschembio.7b00845

Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine. / Anderson, Regan J.; Li, Jasmine; Kedzierski, Lukasz; Compton, Benjamin J.; Hayman, Colin M.; Osmond, Taryn L.; Tang, Ching Wen; Farrand, Kathryn J.; Koay, Hui Fern; Almeida, Catarina Filipa Dos Santos Sa E.; Holz, Lauren R.; Williams, Geoffrey M.; Brimble, Margaret A.; Wang, Zhongfang; Koutsakos, Marios; Kedzierska, Katherine; Godfrey, Dale I.; Hermans, Ian F.; Turner, Stephen J.; Painter, Gavin F.

In: ACS Chemical Biology, Vol. 12, No. 11, 17.11.2017, p. 2898-2905.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine

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AU - Li, Jasmine

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AU - Holz, Lauren R.

AU - Williams, Geoffrey M.

AU - Brimble, Margaret A.

AU - Wang, Zhongfang

AU - Koutsakos, Marios

AU - Kedzierska, Katherine

AU - Godfrey, Dale I.

AU - Hermans, Ian F.

AU - Turner, Stephen J.

AU - Painter, Gavin F.

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