Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Skwarczynski, Mariusz, Zhao, Guangzu, Boer, Jennifer C., Ozberk, Victoria, Azuar, Armira, Cruz, Jazmina Gonzalez, Giddam, Ashwini Kumar, Khalil, Zeinab G., Pandey, Manisha, Shibu, Mohini A., Hussein, Waleed M., Nevagi, Reshma J., Batzloff, Michael R., Wells, James W., Capon, Robert J., Plebanski, Magdalena, Good, Michael F., and Toth, Istvan (2020) Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines. Science Advances, 6 (5). eaax2285.

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Abstract

To be optimally effective, peptide-based vaccines need to be administered with adjuvants. Many currently available adjuvants are toxic, not biodegradable; they invariably invoke adverse reactions, including allergic responses and excessive inflammation. A nontoxic, biodegradable, biocompatible, self-adjuvanting vaccine delivery system is urgently needed. Herein, we report a potent vaccine delivery system fulfilling the above requirements. A peptide antigen was coupled with poly-hydrophobic amino acid sequences serving as self-adjuvanting moieties using solid-phase synthesis, to produce fully defined single molecular entities. Under aqueous conditions, these molecules self-assembled into distinct nanoparticles and chain-like aggregates. Following subcutaneous immunization in mice, these particles successfully induced opsonic epitope-specific antibodies without the need of external adjuvant. Mice immunized with entities bearing 15 leucine residues were able to clear bacterial load from target organs without triggering the release of soluble inflammatory mediators. Thus, we have developed a well-defined and effective self-adjuvanting delivery system for peptide antigens.

Item ID: 63628
Item Type: Article (Research - C1)
ISSN: 2375-2548
Copyright Information: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC APP1132975, NHMRC APP1099999
Date Deposited: 11 Aug 2020 23:57
FoR Codes: 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310113 Synthetic biology @ 33%
31 BIOLOGICAL SCIENCES > 3106 Industrial biotechnology > 310607 Nanobiotechnology @ 33%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 34%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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