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 language | English |
|---|---|
| Pages (from-to) | 2898-2905 |
| Number of pages | 8 |
| Journal | ACS Chemical Biology |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 17 Nov 2017 |
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine
AU - Anderson, Regan J.
AU - Li, Jasmine
AU - Kedzierski, Lukasz
AU - Compton, Benjamin J.
AU - Hayman, Colin M.
AU - Osmond, Taryn L.
AU - Tang, Ching Wen
AU - Farrand, Kathryn J.
AU - Koay, Hui Fern
AU - Almeida, Catarina Filipa Dos Santos Sa E.
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.
PY - 2017/11/17
Y1 - 2017/11/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034645353&partnerID=8YFLogxK
U2 - 10.1021/acschembio.7b00845
DO - 10.1021/acschembio.7b00845
M3 - Article
VL - 12
SP - 2898
EP - 2905
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 11
ER -