Tetravalent Virus-like Particles Engineered To Display Envelope Domain IIIs of Four Dengue Serotypes in Silkworm as Vaccine Candidates.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2025-02-02 DOI:10.1021/acs.biomac.4c01831

Krishna Raja Muthuraman, Jirayu Boonyakida, Mami Matsuda, Ryosuke Suzuki, Tatsuya Kato, Enoch Y Park

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引用次数: 0

Abstract

Dengue virus (DENV) causes dengue fever, the leading mosquito-borne viral disease affecting millions globally. Licensed vaccines have their restrictions, and the development of vaccines is in progress to overcome the limitations. In this study, we expressed two types of virus-like particles (VLPs) and four DENV serotype antigens, 1EDIII-4EDIII (tetEDIII), in silkworm larvae and engineered them into tetravalent VLPs (tetVLPs) displaying tetEDIII. Canine parvovirus-like particles (CPV-LPs) were self-assembled in vivo from viral protein VP2 of CPV (CPV-VP2) as heterologous VLPs; dengue virus capsid-like particles (DENV C-LPs) from capsid protein of DENV serotype 2 (DENV-C2) as homologous VLPs. The tetEDIII was displayed on the surface of CPV-LPs and DENV C-LPs through in vitro SpyTag/SpyCatcher (SpT/SpC) covalent ligation. The EDIII display of CPV-LP is better than that of DENV C-LP. Both tetEDIII-displaying tetravalent CPV-LPs (tetCPV-LPs) and tetravalent DENV C-LPs (tetDENV C-LPs) elicited neutralizing antibodies in BALB/c mice assayed through the single-round infectious particles (SRIP) method. The immunogenicity of tetDENV C-LPs for anti-IgG EDIIIs was higher than that of tetCPV-LPs for serotypes 1 and 3. The neutralization activity of tetDENV C-LPs was higher than that of tetCPV-LPs for D1-SRIP, while tetCPV-LPs were higher than that of tetDENV C-LPs for D2- and D4-SRIP. These results suggest that homologous tetDENV C-LPs and heterologous tetCPV-LPs can be suitable vaccine candidates for further evaluation. This result is the first report to display a tetEDIII on the surface of the DENV C-LPs and the CPV-LPs by in vitro bioconjugation.

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.