Simon H Apte1, Rachel J Stephenson2, Pavla Simerska2, Penny L Groves1, Salwa Aljohani2, Sharareh Eskandari2, Istvan Toth2,3,4, Denise L Doolan1. 1. Infectious Diseases Programme, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia. 2. School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia. 3. School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4012, Australia. 4. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
Abstract
AIM: Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses. MATERIALS & METHODS: Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo. RESULTS: The construct utilizing C12 lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation. CONCLUSION: The C12 polylysine platform was an effective configuration for induction of potent CD8(+) T-cell responses.
AIM: Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses. MATERIALS & METHODS: Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo. RESULTS: The construct utilizing C12lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation. CONCLUSION: The C12polylysine platform was an effective configuration for induction of potent CD8(+) T-cell responses.
Authors: Phurpa Wangchuk; Simon H Apte; Michael J Smout; Penny L Groves; Alex Loukas; Denise L Doolan Journal: Int J Mol Sci Date: 2018-11-06 Impact factor: 5.923
Authors: Gabriel M Hilario; Fernando B Sulczewski; Raquel Liszbinski; Larissa D Mello; Gustavo Hagen; Tiago Fazolo; Jayme Neto; Eliane Dallegrave; Pedro Romão; Tanira Aguirre; Luiz C Rodrigues Junior Journal: IET Nanobiotechnol Date: 2021-03-30 Impact factor: 2.050