A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells

Seesen Mathurin; Jearanaiwitayakul Tuksin; Limthongkul JitraMidoeng PanuwatSunintaboon PanyaUbol Sukathida

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A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells

机译：A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells

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Dengue is the most prevalent mosquito-borne viral disease and continues to be a global public health concern. Although a licensed dengue vaccine is available, its efficacy and safety profile are not satisfac-tory. Hence, there remains a need for a safe and effective dengue vaccine. We are currently developing a bivalent dengue vaccine candidate. This vaccine candidate is composed of a C-terminus truncated non-structural protein 1 (NS11-279) and envelope domain III (EDIII) of DENV-2 encapsidated in the nanocarriers, N, N, N-trimethyl chitosan nanoparticles (TMC NPs). The immunogenicity of this bivalent vaccine candidate was investigated in the present study using BALB/c mice. In this work, we demonstrate that NS1 + EDIII TMC NP-immunized mice strongly elicited antigen-specific antibody responses (anti-NS1 and anti-EDIII IgG) and T-cell responses (NS1-and EDIII-specific-CD4+ and CD8+ T cells). Importantly, the antibody response induced by NS1 + EDIII TMC NPs provided antiviral activities against DENV-2, includ-ing serotype-specific neutralization and antibody-mediated complement-dependent cytotoxicity. Moreover, the significant upregulation of Th1-and Th2-associated cytokines, as well as the increased levels of antigen-specific IgG2a and IgG1, indicated a balanced Th1/Th2 response. Collectively, our find-ings suggest that NS1 + EDIII TMC NPs induced protective responses that can not only neutralize infec-tious DENV-2 but also eliminate DENV-2-infected cells.(c) 2023 The Author(s). Published by Elsevier Ltd.

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《Vaccine》 |2023年第9期|1638-1648|共11页
作者
Seesen Mathurin; Jearanaiwitayakul Tuksin; Limthongkul JitraMidoeng PanuwatSunintaboon PanyaUbol Sukathida;
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作者单位

Mahidol Univ;

Phramongkutklao Hosp;

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正文语种英语
中图分类医学免疫学;
关键词
Bivalent dengue vaccine; Envelope domain III; Non-structural protein 1; Nanoparticle-based vaccine; N; N-trimethyl chitosan; DOMAIN-III; ENVELOPE PROTEIN; VIRUS-INFECTION; NONSTRUCTURAL PROTEIN-1; TRIMETHYL CHITOSAN; ANTIBODY; CD4(+); TYPE-2; NS1;

A bivalent form of nanoparticle-based dengue vaccine stimulated responses that potently eliminate both DENV-2 particles and DENV-2-infected cells

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