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Nanomaterials · 2022 ·Vol. 12 ·期 22 ·3934 · IF 5.719

Development and Efficacy Evaluation of a Novel Nano-Emulsion Adjuvant for a Foot-and-Mouth Disease Virus-like Particles Vaccine Based on Squalane

Xiaoni Shi,Kun Yang,Hetao Song,Zhidong Teng,Yun Zhang,Weihao Ding,Aofei Wang,Shuzhen Tan,Hu Dong,Shiqi Sun,Yonghao Hu,Huichen Guo

The successful development of foot-and-mouth disease virus-like particles (FMD-VLPs) has opened a new direction for researching a novel subunit vaccine for foot-and-mouth disease (FMD). Therefore, it is urgent to develop an adjuvant that is highly effective and safe to facilitate a better immune response to be pair with the FMD-VLP vaccine. In this research, we prepared a new nano-emulsion adjuvant based on squalane (SNA) containing CpG using the pseudo-ternary phase diagram method and the phase transformation method. The SNA consisted of Span85, Tween60, squalane, polyethene glycol-400 (PEG400) and CpG aqueous solution. The average particle diameter of the SNA was about 95 nm, and it exhibited good resistance to centrifugation, thermal stability, and biocompatibility. Then, SNA was emulsified as an adjuvant to prepare foot-and-mouth disease virus-like particles vaccine,BALB/cmice and guinea pigs were immunized, and we evaluated the immunization effect. The immunization results in mice showed that the SNA-VLPs vaccine significantly increased specific antibody levels in mice within 4 weeks, including higher levels of IgG1 and IgG2a. In addition, it increased the levels of IFN-γ and IL-1β in the immune serum of mice. Meanwhile, guinea pig-specific and neutralizing antibodies were considerably increased within 4 weeks when SNA was used as an adjuvant, thereby facilitating the proliferation of splenic lymphocytes. More importantly, in guinea pigs immunized with one dose of SNA-VLPs, challenged with FMDV 28 days after immunization, the protection rate can reach 83.3%, which is as high as in the ISA-206 control group. In conclusion, the novel squalane nano-emulsion adjuvant is an effective adjuvant for the FMD-VLPs vaccine, indicating a promising adjuvant for the future development of a novel FMD-VLPs vaccine.Keywords:nano-emulsion;adjuvants;FMD virus-like particles;squalane;immune responses

CAS / MDL: 26266-57-9
研究领域: 病毒学 · 免疫学 · 药学
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ACS Infectious Diseases · 2023 · IF 5.3

Formulation and Evaluation of Lipidized Imiquimod as an Effective Adjuvant

Wenzhu Yin,Bihua Deng,Zeyu Xu,Haiyan Wang,Fang Ma,Mingxu Zhou,Yu Lu,Jinqiu Zhang

Adjuvants are essential for the induction of robust immune responses against vaccine antigens. Small-molecule TLR7 agonists hold high potential for this purpose. In this communication, imiquimod (IMQ) bearing a cholesterol lipid moiety derivative, IMQ-Chol, was designed and synthesized as a vaccine adjuvant, which could release parent IMQ molecules in aqueous conditions via amide bond hydrolysis. We performed a series of immunological evaluations by cooperating with the inactivated foot-and-mouth disease virus (FMDV). All of the results confirmed that IMQ-Chol could stimulate the body for a prolonged time to produce strong humoral and cellular immunity with a balanced Th1/Th2 immune response through a TLR7-related MAPK pathway. In addition, the results of the proof-of-concept vaccine indicated IMQ-Chol had a good effect on preventing and treating FMD in pigs.

研究领域: 免疫学 · 病毒学 · 药学 · 兽医学
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PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY · 2024 · IF 2.6

Development and efficacy evaluation of a novel water-in-oil-in-water adjuvant for an inactivated foot-and-mouth disease vaccine

Rong,Zhang,Yanming Wei,Xuerong Liu,Yongshu Wu

To develop a novel water-in-oil-in-water (W/O/W) adjuvant and evaluate the effect on foot-and-mouth disease (FMD) inactivated vaccine, in this study, we prepared the novel nano-emulsion adjuvant based on QS-21 (BEA) which is composed of the mixture of mineral oil Marcol52, surfactant Tween80, oleate polyoxyethylene ether ester, polyoxyethylene palmitic acid ester and span80, cosurfactant polyethylene glycol and QS-21. The two-step emulsification method formed the W/O/W nano-emulsion with two films and three-phase structures. The effective particle diameter of the BEA was about 184 nm, and it has good thermal stability. Then, BEA was emulsified as an adjuvant to prepare for the inactivated FMDV vaccine, and BALB/c mice and pigs were immunized to evaluate its safety and immunization effect. The results showed that the inactivated BEA-FMDV vaccine significantly increased BALB/c mice and pigs' antibodies and cytokine IFN-γ in serum. Meanwhile, the pig-neutralizing antibodies were higher than control group. Safety tests found no symptoms of FMD or significant toxic reactions. After 28 days of immunization, the protection rate can reach 93.3%. The BEA vaccine had good stability at 4 °C, no stratification after 180 days, and the content of 146S in the vaccine did not decrease. In conclusion, the BEA prepared in this study is suitable for FMDV inactivated vaccine and is an effective adjuvant.

CAS / MDL: 1338-43-8
研究领域: 兽医学 · 免疫学 · 药学
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MICROBIOLOGY AND IMMUNOLOGY · 2017 ·Vol. 62 ·期 3 ·187-194 · IF 1.706

Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine

Cenrong Zhang,Wei Xu,Jian Chen,Ran Guan,Shicheng Bi,Haibo Jin,Xuemei Cui,Fushan Shi,Songhua Hu

In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1β, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1β in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.

CAS / MDL: 9005-65-6 371-90-4
研究领域: 免疫学 · 兽医学 · 药理学
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Nanoscale Advances · 2023 ·Vol. 5 ·期 5 ·1433-1449 · IF 4.7

Synthesis of a crystalline zeolitic imidazole framework-8 nano-coating on single environment-sensitive viral particles for enhanced immune responses

Liuyang Wang,Xuan Lin,Yanan Sheng,Hongyu Zhu,Zhengjun Li,Zhiguo Su,Rong Yu,Songping Zhang

Encapsulating antigens with zeolitic imidazole framework-8 (ZIF-8) exhibits many advantages in vaccine development. However, most viral antigens with complex particulate structures are sensitive to pH or ionic strength, which cannot tolerate harsh synthesis conditions of ZIF-8. Balancing the viral integrity and the growth of ZIF-8 crystals is crucial for the successful encapsulation of these environment-sensitive antigens in ZIF-8. Here, we explored the synthesis of ZIF-8 on inactivated foot and mouth disease virus (known as 146S), which is easily disassociated into no immunogenic subunits under the existing ZIF-8 synthesis conditions. Our results showed that intact 146S could be encapsulated into ZIF-8 with high embedding efficiency by lowering the pH of the 2-MIM solution to 9.0. The size and morphology of 146S@ZIF-8 could be further optimized by increasing the amount of Zn2+ or adding cetyltrimethylammonium bromide (CTAB). 146S@ZIF-8 with a uniform diameter of about 49 nm could be synthesized by adding 0.01% CTAB, which was speculated to be composed of single 146S armored with nanometer-scale ZIF-8 crystal networks. Plenty of histidine on the 146S surface forms a unique His-Zn-MIM coordination in the near vicinity of 146S particles, which greatly increases the thermostability of 146S by about 5 °C, and the nano-scale ZIF-8 crystal coating exhibited extraordinary stability to resist EDTE-treatment. More importantly, the well-controlled size and morphology enabled 146S@ZIF-8(0.01% CTAB) to facilitate antigen uptake. The immunization of 146S@ZIF-8(4×Zn2+) or 146S@ZIF-8(0.01% CTAB) significantly enhanced the specific antibody titers and promoted the differentiation of memory T cells without adding another immunopotentiator. This study reported for the first time the strategy of the synthesis of crystalline ZIF-8 on an environment-sensitive antigen and demonstrated that the nano-size and appropriate morphology of ZIF-8 are crucial to exert adjuvant effects, thus expanding the application of MOFs in vaccine delivery.

CAS / MDL: 57-09-0
研究领域: 病毒学 · 纳米技术 · 免疫学 · 材料科学 · 药学
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JOURNAL OF MEDICAL VIROLOGY · 2019 ·Vol. 91 ·期 6 ·941-948 · IF 2.049

Hollow mesoporous silica nanoparticles as delivery vehicle of foot-and-mouth disease virus-like particles induce persistent immune responses in guinea pigs

Manyuan Bai,Hu Dong,Xin Su,Ye Jin,Shiqi Sun,Yingpeng Zhang,Yunshang Yang,Huichen Guo

Foot-and-mouth disease (FMD) is an acute and febrile infectious disease, which can cause great economic losses. Virus-like particles (VLPs) as an advantageous antigen can induce significant specific immune response. To improve immunity of VLPs, especially, make it induce persistent immune response, the hollow mesoporous silica nanoparticles (HMSNs) as a potential nano-adjuvant were synthesized and loaded the FMD virus (FMDV) VLPs. They were injected into guinea pigs and the specific immune response was detected. The results confirmed that HMSNs/VLPs can induce persistent humoral immunity with high-level antibody titer for more than three months. HMSNs also improve the T-lymphocyte proliferation and IFN-γ induced by FMDV VLPs, and provides the ideal protection against FMDV challenge. These consequences indicated that HMSNs were good protein delivery vehicle and potential nano-adjuvant of vaccines. Highlights We synthesized Hollow mesoporous silica nanoparticles (HMSNs), as a delivery vehicle, are ideal candidate and have many unique structural features, including relatively larger surface areas, and controlled release capability, especially, good biocompatibility compared to golden nanoparticles as adjuvant. VLPs are composed of one or more structural proteins of virus, and without viral genetic material. As a new type of safe vaccine, FMDV VLPs can induce excellent immune response as traditional vaccines. To improve specific and persistent immune responses of FMDV VLPs, It is first time that HMSN was used as delivery of FMDV VLPs. The results confirmed that HMSNs can improve specific and persistent immune responses of FMDV VLPs, as new generation adjuvant.

CAS / MDL: 78-10-4
研究领域: 纳米技术 · 免疫学 · 病毒学 · 兽医学
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