Zhao, Guangzu, Sathkumara, Harindra D., Miranda-Hernandez, Socorro, Seifert, Julia, Valencia Hernandez, Ana Maria, Puri, Munish, Huang, Wenbin, Toth, Istvan, Daly, Norelle, Skwarczynski, Mariusz, and Kupz, Andreas (2025) A Modular Self-Assembling and Self-Adjuvanting Multiepitope Peptide Nanoparticle Vaccine Platform to Improve the Efficacy and Immunogenicity of BCG. Small, 21 (7). 2406874.

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Abstract

After more than a century since its initial development, Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered a viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated on recombinant proteins, here we developed a novel modular peptide-based subunit vaccine platform that is flexible, cold-chain independent and customizable to diverse circumstances and populations. Each individual peptide building block consists of a linear arrangement comprising a 15-leucine self-assembly inducer moiety, a Mycobacterium tuberculosis (Mtb) target epitope and an human leukocyte antigen E (HLA-E) binding moiety, with each moiety separated by a triple lysine spacer. The building blocks, in any combination, are able to form a multiepitope nanoparticle. Six Mtb epitopes were selected to produce the self-assembling and self-adjuvating peptide-based TB nano-vaccine candidate PNx6. In vivo vaccination-challenge experiments demonstrated that subcutaneous boost of parenteral BCG immunization with PNx6 significantly enhanced its immunogenicity and improved its protective efficacy in a murine model of TB by more than 5-fold. This study presents evidence that purely amphiphilic peptides self-assemble into self-adjuvating nanoparticles with appropriate size and morphology for TB vaccination with great potential for a multitude of other diseases.

Item ID:	86512
Item Type:	Article (Research - C1)
ISSN:	1613-6829
Copyright Information:	© 2025 Wiley-VCH GmbH
Funders:	National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants:	NHMRC Ideas (APP2001262), NHMRC Investigator Grant (APP2008715), ARC Discovery Project (DP21010280)
Date Deposited:	05 Aug 2025 03:10
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 30% 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 40% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 30%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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