Development of a Novel Polyleucine‐Based Immunopotentiator for Subunit Vaccines Against Group A Streptococcus
Year: 2026
Type: article
Abstract: ABSTRACT Mixture‐based vaccine formulations offer distinct advantages by eliminating the need for chemical conjugation or complex encapsulations, thereby streamlining preparation, enhancing versatility, and reducing cost and production time. In this study, we report the design of a novel polypeptide‐based self‐assembling adjuvant where a water insoluble 15‐mer polyleucine (L 15 ) is coupled with a polylysine unit (K 6 ). As a nano adjuvant, L 15 K 6 markedly enhances antigen uptake by dendritic cells, promotes antigen‐presenting cell maturation (CD40, CD80/86, and MHC‐II), and upregulates Toll‐like receptor expression, particularly Toll‐like receptor 4 in dendritic cells. Bulk RNA sequencing further reveals robust NF‐κB pathway activation by L 15 K 6 . When co‐delivered with peptide or protein antigens derived from Group A Streptococcus, L 15 K 6 induces robust antigen‐specific IgG response with highly potent antibacterial activity against two clinical Group A Streptococcus strains in vitro. Beyond antigens derived from Group A Streptococcus, L 15 K 6 also enhances immune responses against model protein antigens such as ovalbumin and bovine serum albumin, highlighting its broad applicability. Notably, a single immunization with L 15 K 6 outperforms alum adjuvant in eliciting high levels of bovine serum albumin‐specific IgG. These findings establish L 15 K 6 as a simple yet powerful immunopotentiator with significant promise for the development of broadly applicable subunit vaccines.
Source: Small
Authors: Lantian Lu, Jazmina L. Gonzalez Cruz, Rabina Giri, Yuexiao Zhang, Sahra Bashiri, Leslie C. Domínguez Cadena, Shuhang Li, Zeinab G. Khalil, Waleed M. Hussein, Jingwen Wang, Jolynn Kiong, Xuehan Lu, Jiahui Zhang, Miao Lu, Wenbin Huang, Wei Yang Kong, Ummey Jannatun Nahar, Prashamsa Koirala, Zhong Guo, Patricia Walden, Antje Blumenthal, Jakob Begun, Kirill Alexandrov, Istvan Toth, Rachel J. Stephenson, Mariusz Skwarczynski
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Awards: G113630290, G1883421761, Towards the sustainable discovery and development of new antibiotics, Artificial protein circuits and the next generation diagnostics, New Frontiers in Innate Immunity, ARC Centre of Excellence in Synthetic Biology, A nanonaccine against Invasive Group A Streptococcus and Rheumatic Heart Disease
OpenAlex ID: W7129332672