Polyphenylalanine as a self-adjuvanting delivery system for peptide-based vaccines: the role of peptide conformation
Mariusz Skwarczynski
A # , Guangzu Zhao A # , Victoria Ozberk B , Ashwini Kumar Giddam B , Zeinab G. Khalil B , Manisha Pandey B , Waleed M. Hussein A , Reshma J. Nevagi A , Michael R. Batzloff B , Robert J. Capon C , Michael F. Good B and Istvan Toth A C D *
+ Author Affiliations
- Author Affiliations
A School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, Qld 4072, Australia.
B Institute for Glycomics, Griffith University, Gold Coast, Qld 4222, Australia.
C Institute for Molecular Bioscience, The University of Queensland, St Lucia, Qld 4072, Australia.
D School of Pharmacy, The University of Queensland, Woolloongabba, Qld 4102, Australia.
* Correspondence to: i.toth@uq.edu
# These authors contributed equally to this paper
Handling Editor: Mibel Aguilar
Australian Journal of Chemistry 76(8) 429-436 https://doi.org/10.1071/CH22167
Submitted: 29 July 2022 Accepted: 3 October 2022 Published: 8 December 2022
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)
Abstract
Peptide-based vaccines are composed of minimal microbial components that are required to stimulate immune responses. Peptide antigens are easy to produce, relatively cheap and non-toxic. They are also able to activate the immune system in a well-controlled manner. However, peptides themselves are poor immunogens and have to be co-administered with an adjuvant (immune stimulator) to produce desired immune responses. Unfortunately, many adjuvants are toxic, poorly effective or not compatible with peptide antigens. Recently, we demonstrated that, upon conjugation to a peptide antigen, poly(hydrophobic amino acids) can self-assemble into nanoparticles and induce strong humoral immune responses. Here, we examine the ability of polyphenylalanine to act as a self-adjuvanting moiety when conjugated to a peptide antigen derived from Group A Streptococcus M-protein. The polyphenylalanine moiety was further lipidated to alter the conjugate conformation and its ability to form nanoparticles. The lipidated analogue triggered the production of a high level of antibodies in immunized mice. The antibodies produced were highly opsonic against tested GAS clinical isolates.
Keywords: adjuvant, amino acid polymers, epitope conformation, Group A Streptococcus, nanoparticles, opsonic antibodies, peptide self-assembly, peptide vaccine.
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