EPIclip: A Novel Approach for the Production of Decorated Virus-Like Particles Mediated by High-Affinity Protein Binding Partners

TY - JOUR

T1 - EPIclip

T2 - A Novel Approach for the Production of Decorated Virus-Like Particles Mediated by High-Affinity Protein Binding Partners

AU - Moleda, Aleksandra

AU - Bagshaw, Olivia

AU - Repkewitz, Jonas

AU - Ahmed, Suaad

AU - Jakab, Attila

AU - Gomez Jordan, Pamela

AU - Sunny, Sherin

AU - Bourdon, Jean-Christophe

AU - Foerster, John

N1 - Copyright: © 2026 by the authors.

PY - 2026/1/28

Y1 - 2026/1/28

N2 - Background: Virus-like particles (VLPs) represent key tools for the development of vaccines due to their ability to induce a potent immune response to epitopes presented on their surface. However, the decoration of VLPs with a complete heterologous protein on the surface remains a bottleneck for clinical translation due to the complexity of manufacture. We present a novel platform, EPIclip™, for the decoration of VLPs mediated by high-affinity protein binding partners, colicin E7 (ColE7) and immunity protein 7 (Im7), within a single prokaryotic host. We evaluate this approach using a modified hepatitis B core capsid protein and IL-31 as a model epitope. IL-31 is a prominent therapeutic target for the development of pruritic diseases.Methods: We explore the design and development of the platform, including the use of T-cell-stimulating peptides. We demonstrate several small-scale purification methods for the candidate VLP, as well as morphological analysis by transmission electron microscopy (TEM). Further, we vaccinate mice with IL-31-displaying VLPs to evaluate immunogenicity and the ability to prevent IL-31-induced pruritus in vivo.Results: Our results demonstrate that decorated VLPs dosed in mice elicit an IgG response against IL-31 with at least six months of durability. In addition, IL-31-displaying VLPs suppress the development of IL-31-induced pruritus, confirming in vivo target neutralisation. Notably, IL-31-displaying VLPs induce a strong T-cell response against the VLP capsid but not against the cytokine, confirming a B-cell-biased immune response and the absence of detrimental autoreactive T cells. We further demonstrate the translation of this system with an additional virus capsid: tomato aspermy virus (TAV).Conclusions: Taken together, the novel EPIclip™ platform may represent a promising therapeutic approach for pruritic diseases. Additionally, this modular system could be adapted for a wide range of research as well as human and veterinary therapeutic applications.

AB - Background: Virus-like particles (VLPs) represent key tools for the development of vaccines due to their ability to induce a potent immune response to epitopes presented on their surface. However, the decoration of VLPs with a complete heterologous protein on the surface remains a bottleneck for clinical translation due to the complexity of manufacture. We present a novel platform, EPIclip™, for the decoration of VLPs mediated by high-affinity protein binding partners, colicin E7 (ColE7) and immunity protein 7 (Im7), within a single prokaryotic host. We evaluate this approach using a modified hepatitis B core capsid protein and IL-31 as a model epitope. IL-31 is a prominent therapeutic target for the development of pruritic diseases.Methods: We explore the design and development of the platform, including the use of T-cell-stimulating peptides. We demonstrate several small-scale purification methods for the candidate VLP, as well as morphological analysis by transmission electron microscopy (TEM). Further, we vaccinate mice with IL-31-displaying VLPs to evaluate immunogenicity and the ability to prevent IL-31-induced pruritus in vivo.Results: Our results demonstrate that decorated VLPs dosed in mice elicit an IgG response against IL-31 with at least six months of durability. In addition, IL-31-displaying VLPs suppress the development of IL-31-induced pruritus, confirming in vivo target neutralisation. Notably, IL-31-displaying VLPs induce a strong T-cell response against the VLP capsid but not against the cytokine, confirming a B-cell-biased immune response and the absence of detrimental autoreactive T cells. We further demonstrate the translation of this system with an additional virus capsid: tomato aspermy virus (TAV).Conclusions: Taken together, the novel EPIclip™ platform may represent a promising therapeutic approach for pruritic diseases. Additionally, this modular system could be adapted for a wide range of research as well as human and veterinary therapeutic applications.

KW - expression system

KW - interleukin-31

KW - vaccine development

KW - virus-like particles

U2 - 10.3390/vaccines14020129

DO - 10.3390/vaccines14020129

M3 - Article

C2 - 41746052

SN - 2076-393X

VL - 14

JO - Vaccines

JF - Vaccines

IS - 2

M1 - 129

ER -