Recombinant lipidated dengue-3 envelope protein domain III stimulates broad immune responses in mice. Issue 8 (17th February 2016)

• Record Type: Journal Article
• Authors: Chiang, Chen-Yi; Liu, Shih-Jen; Hsieh, Chun-Hsiang; Chen, Mei-Yu; Tsai, Jy-Ping; Liu, Hsueh-Hung; Chen, I.-Hua; Chong, Pele; Leng, Chih-Hsiang; Chen, Hsin-Wei
• Is Part Of: Vaccine. Volume 34:Issue 8(2016)
• Page Start: 1054
• Page End: 1061
• Publication Date: 2016-02-17
• Subjects: Dengue virus -- Envelope protein domain III -- Lipoprotein -- Vaccine; D3ED III ecombinant dengue-3 envelope protein domain III -- ED III/Alum D3ED III formulated with aluminum phosphate -- FFU focus-forming unit -- FRNT focus reduction neutralization tests -- IMAC immobilized metal affinity chromatography -- LD3ED III recombinant lipidated dengue-3 envelope protein domain III; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.01.009
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Lipidated dengue-3 envelope protein domain III can induce broad profiles of cellular and humoral immune responses. Lipidated dengue-3 envelope protein domain III stimulates neutralizing antibody responses without exogenous adjuvants. Viremia levels are reduced in mice immunized with lipidated dengue-3 envelope protein domain III. Abstract: The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope protein domain III (D3ED III) in lipidated form using an Escherichia coli -based system. The recombinant lipidated dengue-3 envelope protein domain III (LD3ED III) augments the expression levels of IL-12 family cytokines. LD3ED III-immunized mice enhance wide ranges of T cell responses as indicated by IFN-γ, IL-17, IL-21 production. Additionally, LD3ED III-immunized mice increase the frequencies of anti-D3ED III antibody producing cells. The boosted antibody titers cover various IgG isotypes, including IgG1, IgG2a, IgG2b, and IgG3. Importantly, LD3ED III-immunized mice induce neutralizing antibody capacity associated with a reduction of viremia levels after challenges. In contrast, mice that are immunized with D3ED III formulated with aluminum phosphate (D3ED III/Alum) only enhance Th2 responses and boost IgG1 antibody titers. Neither neutralizing antibody responses nor the inhibition of viremia levels after challenge is observed in mice that are immunized with D3ED III/Alum. These results suggest that LD3ED III can induce broad profiles of cellular and humoral immune responses.