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Lipid A analog CRX-527 conjugated to synthetic peptides enhances vaccination efficacy and tumor control.


ABSTRACT: Adjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of the most potent immune-stimulators known, and is recognized via Toll-like receptor 4 (TLR4). In this study, we explore the use of the synthetic, non-toxic, lipid A analog CRX-527 as an adjuvant for peptide cancer vaccines. This well-defined adjuvant was covalently conjugated to antigenic peptides as a strategy to improve vaccine efficacy. We show that coupling of this TLR4 agonist to peptide antigens improves vaccine uptake by dendritic cells (DCs), maturation of DCs and T cell activation in vitro, and stimulates DC migration and functional T cell priming in vivo. This translates into enhanced tumor protection upon prophylactic and therapeutic vaccination via intradermal injection against B16-OVA melanoma and HPV-related TC1 tumors. These results highlight the potential of CRX-527 as an adjuvant for molecularly defined cancer vaccines, and support the design of adjuvant-peptide conjugates as a strategy to optimize vaccine formulation.

SUBMITTER: Tondini E 

PROVIDER: S-EPMC9226002 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Lipid A analog CRX-527 conjugated to synthetic peptides enhances vaccination efficacy and tumor control.

Tondini Elena E   Reintjens Niels R M NRM   Castello Giulia G   Arakelian Tsolere T   Isendoorn Marjolein M   Camps Marcel M   Vree Jana J   van der Marel Gijs A GA   Filippov Dmitri V DV   Codee Jeroen D C JDC   Ossendorp Ferry F  

NPJ vaccines 20220623 1


Adjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of the most potent immune-stimulators known, and is recognized via Toll-like receptor 4 (TLR4). In this study, we explore the use of the synthetic, non-toxic, lipid A analog CRX-527 as an adjuvant for peptide cancer vaccines. This well-defined adjuvant was covalently conjugated to antigenic peptides as a strategy to improve vaccine efficacy. We sh  ...[more]

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