The influence of physicochemical properties of lipopeptide adjuvants on immune response: a rationale for engineering a potent vaccine

Eskandari, Sharareh, Pattinson, David J., Stephenson, Rachel J., Groves, Penny L., Apte, Simon H., Sedaghat, Bita, Chandurudu, Saranya, Doolan, Denise L., and Toth, Istvan (2018) The influence of physicochemical properties of lipopeptide adjuvants on immune response: a rationale for engineering a potent vaccine. Chemistry: a European journal, 24. pp. 9892-9902.

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Abstract

Adjuvant development and understanding the physicochemical properties of particles and interpreting the subsequent immunological responses is a challenge faced by many researchers in the vaccine field. We synthesized and investigated the physicochemical properties and immunogenicity of a library of multiple epitope self-adjuvant lipopeptides in a novel asymmetric arrangement. Vaccine candidates were synthesized using a combination of solid phase peptide synthesis and copper-mediated click chemistry. In-vivo studies showed that vaccine constructs containing a single OVA CD8+ T cell epitope and two N-terminally located C16 lipid moieties were more effective at generating robust cellular immune responses compared with the same molecule containing multiple copies of the OVA CD8+ T cell epitope with or without the C16 moieties. Furthermore, attachment of the two C16 lipids to the N-terminus provoked formation of long β-sheet fibrils and was shown to induce a higher CD8+ donor T cell frequency and IFN-ɣ secretion, compared to vaccine constructs with an internal lipid placement. A regression analysis indicated that particle secondary structure had a significant impact on CD8+ donor T cell frequency and cytolytic activity. In addition, IFN-ɣ production was influenced significantly by particle shape. The findings of this reaserch will impact the future deisgn of vaccine intended to elict cellular immune responses.

Item ID: 53733
Item Type: Article (Research - C1)
ISSN: 1521-3765
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC grant APP1037304
Date Deposited: 22 Aug 2018 03:16
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030406 Proteins and Peptides @ 60%
03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030405 Molecular Medicine @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 20%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920412 Preventive Medicine @ 80%
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