Alternative antigen retention by a gp96-fusion approach induces long-lasting and broad immunity in mice.

ingentiumby ingentium

In Vaccines Literature.

Alternative antigen retention by a gp96-fusion approach induces long-lasting and broad immunity in mice.

Publication date: Dec 17, 2025

Efficient antigen delivery to B cells and dendritic cells (DC) is critical for enhancing vaccine immunogenicity. Here, we develop a dimeric vaccine strategy by fusing antigens to the N-terminal of heat shock protein GP96. This platform generates compact, nanoscale particles that fully exposed antigenic sites. We validate the vaccine strategy using the SARS-CoV-2 receptor-binding domain (RBD) antigen in a viral challenge model with hACE2 mice and the human papillomavirus (HPV) E7 protein in a HeLa xenograft model with nude mice. The GP96 moiety directly bound its receptor, LRP1, thereby enhancing antigen accumulation on follicular DCs and prolonging lymph node retention, ultimately amplifying germinal center B cell responses. Furthermore, GP96-LRP1 interaction on DCs promotes antigen endocytosis, underpinning epitope presentation and robust cross-conserved T cell activation. Consequently, this design induces potent, durable humoral immunity, cross-conserved T cell responses, and pulmonary mucosal immunity, underscoring its promise as a versatile and effective vaccination strategy.

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Concepts Keywords
Efficient Alternative
Mice Antigen
Mucosal Conserved
Vaccines Cross
Xenograft Dcs
Enhancing
Gp96
Immunity
Induces
Lrp1
Mice
Receptor
Responses
Retention
Vaccine

Semantics

Type Source Name
disease MESH shock
drug DRUGBANK Cycloserine
disease MESH DCs
pathway KEGG Endocytosis
pathway REACTOME Reproduction
disease MESH included
disease MESH CAS
drug DRUGBANK Coenzyme M
disease MESH influenza
disease MESH viral infections
pathway REACTOME Release
disease MESH strains
disease MESH tumor
drug DRUGBANK Aluminium
disease MESH NTD
drug DRUGBANK Trypsin
disease MESH ADCC
disease MESH weight loss
disease MESH bronchopneumonia
disease MESH interstitial pneumonia
drug DRUGBANK N-acetylsulfanilyl chloride
pathway REACTOME Metabolism
disease MESH APC
disease MESH LNs
disease MESH FDC
drug DRUGBANK Proline
drug DRUGBANK Amino acids
drug DRUGBANK Alpha-Linolenic Acid
disease MESH ICS
drug DRUGBANK Tretamine
pathway REACTOME Autophagy
pathway KEGG Lysosome
pathway KEGG Proteasome
disease MESH body weight
disease MESH LPS
pathway REACTOME Translation
drug DRUGBANK Water
drug DRUGBANK Carbon dioxide
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Park
disease MESH FBS
drug DRUGBANK Benzylpenicillin
drug DRUGBANK Streptomycin
drug DRUGBANK Amber
drug DRUGBANK Isoxaflutole
drug DRUGBANK Flunarizine
disease MESH PME
drug DRUGBANK Tromethamine
drug DRUGBANK Potassium Chloride
disease MESH PBS
drug DRUGBANK Silicon dioxide
drug DRUGBANK L-Tryptophan
drug DRUGBANK L-Tyrosine
drug DRUGBANK Aspartame
disease MESH Image
drug DRUGBANK Phosphate ion
drug DRUGBANK Aluminum hydroxide
drug DRUGBANK Isoflurane
drug DRUGBANK Human Serum Albumin
disease MESH infection
drug DRUGBANK Formaldehyde
disease MESH HTS
drug DRUGBANK Sodium bicarbonate
disease MESH AEC
drug DRUGBANK Fluorescein
pathway REACTOME Digestion
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
drug DRUGBANK Dimercaprol
disease MESH dissociation
drug DRUGBANK Collagenase clostridium histolyticum
disease MESH Papilloma
disease MESH necrosis
disease MESH pain
disease MESH lethargy
drug DRUGBANK BIA
disease MESH COVID 19
disease MESH Death
disease MESH Dis
drug DRUGBANK Guanosine
disease MESH gliomas
disease MESH genital warts
pathway REACTOME Influenza Infection
drug DRUGBANK Methylergometrine
drug DRUGBANK Paclitaxel
disease MESH hepatocellular carcinoma
pathway KEGG Hepatocellular carcinoma
pathway KEGG Glioma
drug DRUGBANK Vitespen
disease MESH melanoma
pathway KEGG Melanoma
drug DRUGBANK Etoperidone
disease MESH SNE
drug DRUGBANK Albendazole

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