Influence of Physicochemical Properties of Lipopeptide Adjuvants on the Immune Response: A Rationale for Engineering a Potent Vaccine

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Eskandari, Sharareh
Pattinson, David J
Stephenson, Rachel J
Groves, Penny L
Apte, Simon H
Sedaghat, Bita
Chandurudu, Saranya
Doolan, Denise L
Toth, Istvan
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2018
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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 to 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‐γ 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‐γ production was influenced significantly by particle shape. The findings of this research will impact the future design of a vaccine intended to elicit cellular immune responses.

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Chemistry - A European Journal

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24

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39

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NHMRC

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APP1037304

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© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: Influence of Physicochemical Properties of Lipopeptide Adjuvants on the Immune Response: A Rationale for Engineering a Potent Vaccine, Chemistry - A European Journal, Publication cover image Volume24, Issue39, 2018 which has been published in final form at https://doi.org/10.1002/chem.201801378. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)

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Chemical sciences

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