A spontaneously formed and self-adjuvanted hydrogel vaccine triggers strong immune responses

He, Tao; Liang, Xiuqi; Lu, Li-Fan; Gong, Songlin; Li, Xinchao; Zhang, Miaomiao; Zhu, Shunyao; Xiao, Haitao; Wu, Qinjie; Gong, Changyang

doi:10.1016/j.matdes.2020.109232

Cited by 35 publications

(25 citation statements)

References 36 publications

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“…These data clearly exemplified the presence and specificity of the growth-inhibitory antibodies induced by rFu24 formulated with peptide-based hydrogels. These hydrogels compared well with other peptide-based hydrogels reported as antigen delivery system and immunostimulatory agents [ 60 , 66 , 67 ]. The hydrogels described in this study are more attractive, since they are based on a dipeptide structure, also easy to make and characterize.…”

Section: Discussionmentioning

confidence: 61%

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels

et al. 2021

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A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a recombinant fusion chimera protein, His-tagged PfMSP-Fu24, by producing it as a tag-free recombinant protein. In this study, tag-free recombinant PfMSPFu24 (rFu24) was expressed in Escherichia coli, and the soluble protein was purified using a three-step purification involving ammonium sulphate precipitation followed by 2-step ion exchange chromatography procedures and shown that it was highly immunogenic with the human-compatible adjuvant Alhydrogel. We further investigated two dipeptides, phenylalanine-α, β-dehydrophenylalanine (FΔF) and Leucine-α, β-dehydrophenylalanine (LΔF) based hydrogels as effective delivery platforms for rFu24. These dipeptides self-assembled spontaneously to form a highly stable hydrogel under physiological conditions. rFu24 was efficiently entrapped in both the F∆F and L∆F hydrogels, and the three-dimensional (3D) mesh-like structures of the hydrogels remained intact after the entrapment of the antigen. The two hydrogels significantly stimulated rFu24-specific antibody titers, and the sera from the immunized mice showed an invasion inhibitory activity comparable to that of Alhydrogel. Easily synthesized dipeptide hydrogels can be used as an effective antigen delivery platform to induce immune responses.

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Section: Discussionmentioning

confidence: 61%

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels

et al. 2021

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“…The uniqueness of thermosensitive hydrogel systems is that they spontaneously form gels through temperature stimulation and then transfer antigens or vaccines to the target physiological area, thereby improving system efficiency by enhancing immunogenicity and promoting antigen-mediated immunity as an adjuvant. Moreover, hydrogel polymer matrices can degrade in a physiological system [81]. Antitumor immunotherapy vaccine treatment has become an important means to inhibit tumor recurrence and metastases.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy

et al. 2022

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Thermosensitive hydrogels, having unique sol–gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.

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“…These carbohydrates have been formulated as nanoparticles, gels, and antigen-fusion complexes to improve both humoral and cellular immune responses to vaccines. These approaches have yielded promising pre-clinical results, including the induction of a balanced immune response and antigen dose sparing [ 94 , 95 , 96 , 97 ]. There are several ongoing and completed clinical trials investigating the safety and efficacy of carbohydrate adjuvants for infectious disease and cancer, such as chitosan (NCT00806962), β-glucan (NCT04936529), mannan [ 98 ], and crystalline δ-inulin under the trademark Advax TM (NCT05005559) [ 94 ], which have thus far suggested carbohydrate adjuvants can be well-tolerated and effective in humans at the doses necessary to confer an immunological benefit [ 98 , 99 , 100 ].…”

Section: Adjuvants With New Targetsmentioning

confidence: 99%

Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness

Pogostin

McHugh

2021

Bioengineering

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Future infectious disease outbreaks are inevitable; therefore, it is critical that we maximize our readiness for these events by preparing effective public health policies and healthcare innovations. Although we do not know the nature of future pathogens, antigen-agnostic platforms have the potential to be broadly useful in the rapid response to an emerging infection—particularly in the case of vaccines. During the current COVID-19 pandemic, recent advances in mRNA engineering have proven paramount in the rapid design and production of effective vaccines. Comparatively, however, the development of new adjuvants capable of enhancing vaccine efficacy has been lagging. Despite massive improvements in our understanding of immunology, fewer than ten adjuvants have been approved for human use in the century since the discovery of the first adjuvant. Modern adjuvants can improve vaccines against future pathogens by reducing cost, improving antigen immunogenicity, and increasing antigen stability. In this perspective, we survey the current state of adjuvant use, highlight potentially impactful preclinical adjuvants, and propose new measures to accelerate adjuvant safety testing and technology sharing to enable the use of “off-the-shelf” adjuvant platforms for rapid vaccine testing and deployment in the face of future pandemics.

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A spontaneously formed and self-adjuvanted hydrogel vaccine triggers strong immune responses

Cited by 35 publications

References 36 publications

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy

Novel Vaccine Adjuvants as Key Tools for Improving Pandemic Preparedness

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