Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice

Ren, Zhiguang; Zhao, Yongkun; Liu, Jing; Ji, Xianliang; Meng, Lingnan; Wang, Tiecheng; Sun, Wenzhao; Zhang, Kun; Sang, Xiaoyu; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Hualei; Wang, Cuiling; Yang, Zhengyan; Wang, Zhizeng; Gao, Yuwei; Xia, Xianzhu

doi:10.1016/j.vaccine.2018.08.053

Cited by 16 publications

(10 citation statements)

References 40 publications

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“…VLPs have been produced in a wide range of taxonomically and structurally distinct viruses, combining unique advantages in terms of safety and immunogenicity as exemplified by the current vaccines against the Human Papilloma Virus (HPV) and Hepatitis B virus (HBV) 17,18 . On the other hand, although several routes of administration have been used in different vaccination trials with VLPs, including nasal 46 , intravaginal 33 , rectal 47 , skin 48 , and oral 49 routes, VLP vaccines that are available on the market have only been delivered parenterally, showing the same disadvantages that any other vaccine given by injection 18 . Therefore, we hypothesized that harnessing VLP vaccines with VSPs could allow their oral administration while providing adjuvant properties.…”

Section: Discussionmentioning

confidence: 99%

Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

et al. 2019

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Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host’s intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.

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Section: Discussionmentioning

confidence: 99%

Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

et al. 2019

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“…Flagellin was reported to activate human DCs, resulting in up-regulation of maturation markers and chemokine production via a TLR5 signaling [35], suggesting its potential vaccine adjuvant mechanism. Also, previous studies demonstrated that influenza VLPs copresenting flagellin and hemagglutinin antigens were more effective in inducing virusspecific Th1-biased humoral immune responses than VLP vaccines without flagellin [25,26,36,37]. Herein, we investigated whether flagellin only expressing VLP (FliC-VLP) would be an independent and effective vaccine adjuvant to promote the immune responses to coadministered vaccine antigens in wild-type and mutant mice in comparison with soluble flagellin.…”

Section: Discussionmentioning

confidence: 99%

Flagellin-expressing virus-like particles exhibit adjuvant effects on promoting IgG isotype-switched long-lasting antibody induction and protection of influenza vaccines in CD4-deficient mice

Lee

et al. 2019

Vaccine

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Incorporation of membrane-anchored flagellin molecules into the surfaces of influenza virus-like particles (VLP) was previously reported to promote T helper (Th) 1 IgG antibody production and protective efficacy of co-presented vaccine antigens. Herein, we investigated the potential adjuvant effects and mechanisms of flagellin-expressing VLP (FliC-VLP) as an independent component on influenza vaccination in wild-type and mutant mouse models. FliC-VLP adjuvanted influenza vaccination was highly effective in promoting the induction of Th1-biased IgG isotype switched antibodies, enhanced protection, and long-lasting IgG antibody responses in both wild-type and CD4-knockout mice. In contrast, the adjuvant effects of soluble flagellin were Th2-biased and required CD4 T helper cells. The adjuvant effects of FliC-VLP were less dependent on CD4 T cells and flagellin-mediated innate immune signaling pathways. The results suggest that FliC-VLP might play an effective adjuvant role in an immune competent condition as well as in a defect of CD4 T cells.

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“…Oral administration of flagellin-based vaccines could induce effective immune protection in mice. In the study by Ren et al [ 39 ], the H5N1 chimeric virus-like particles (VLPs) containing membrane-anchored FliC (FliC-VLP) were administered orally to mice, and the virus-specific IgG titers of immunized mice were tenfold higher than those of mice immunized with H5N1-VLPs lacking FliC, which significantly improved the protective immune response to lethal challenge from both homologous and heterologous H5N1 viruses. According to Zhou et al [ 34 ], mice orally inoculated with LBNSE-Flagellin (the recombinant rabies viruses [rRABV] expressing flagellin of Salmonella enterica subsp.)…”

Section: Biogenic Type Oral Vaccine Adjuvantsmentioning

confidence: 99%

Current Progress and Challenges in the Study of Adjuvants for Oral Vaccines

Yang

et al. 2023

BioDrugs

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Over the past 20 years, a variety of potential adjuvants have been studied to enhance the effect of oral vaccines in the intestinal mucosal immune system; however, no licensed adjuvant for clinical application in oral vaccines is available. In this review, we systematically updated the research progress of oral vaccine adjuvants over the past 2 decades, including biogenic adjuvants, non-biogenic adjuvants, and their multi-type composite adjuvant materials, and introduced their immune mechanisms of adjuvanticity, aiming at providing theoretical basis for developing feasible and effective adjuvants for oral vaccines. Based on these insights, we briefly discussed the challenges in the development of oral vaccine adjuvants and prospects for their future development.

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Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice

Cited by 16 publications

References 40 publications

Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

Flagellin-expressing virus-like particles exhibit adjuvant effects on promoting IgG isotype-switched long-lasting antibody induction and protection of influenza vaccines in CD4-deficient mice

Current Progress and Challenges in the Study of Adjuvants for Oral Vaccines

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