Immune-enhanced EV71 vaccine soluble microneedle

Abstract

The invention discloses an immune-enhanced EV71 vaccine soluble microneedle which comprises a needle body and a backing, the needle body is composed of an EV71 vaccine, an adjuvant and a matrix material, the adjuvant is a mixture of CPG-ODN and notoginsenoside Rb1, and the content ratio of the EV71 vaccine to the adjuvant to the matrix material is 1: 30: 69. By selecting a specific adjuvant (the combination of CPG-ODN and notoginsenoside Rb1), a specific content ratio of the EV71 vaccine to the adjuvant and a proper drug loading capacity, the prepared EV71 vaccine soluble microneedle can significantly enhance immunogenicity and has good mechanical properties.

Description

technical field [0001] The invention relates to the technical field of administration of hand-foot-mouth vaccine, in particular to an immune-enhanced EV71 vaccine soluble microneedle. Background technique [0002] Hand, foot and mouth disease is an infectious disease caused by enteroviruses, and cases have been found all over the world in recent years. The disease is mostly found in children under the age of 5, which can cause fever, rashes and ulcers on the hands, feet, mouth and other parts. In severe cases, it can cause complications such as myocarditis, pulmonary edema, and aseptic meningoencephalitis. And there are various types of viruses that cause the disease. More than 20 types of viruses have been found to cause the disease, of which Coxsackie virus A16 (Cox A16) and enterovirus 71 (EV71) are the most common. At present, the EV71 inactivated vaccine that has been marketed in my country has few adverse reactions, but there are also problems such as easy destruction...

AI Technical Summary

Problems solved by technology

The adjuvants used in EV71 vaccines currently on the market are all aluminum adjuvants, and aluminum adjuvants have defects such as inability to induce cytotoxic T cell responses, induce inflammation and other adverse reactions, and are not suitable for recombinant protein or subunit vaccines (Zhou Yang, Geng Xingchao, Wang Jufeng et al. The latest research progress on vaccine adjuvants [J]. China New Drugs, 2013 (1): 34-42), and referring to the amount of aluminum adjuvant in the injection, it is difficult to prepare microneedles

In addition, there are few literatures on the application of adjuvants in hand-foot-mouth vaccines. For example, it is reported that using MF59 adjuvant to load EV71 inactivated vaccine (Zhang Xuemei. MF59 adjuvant can induce humoral immune response of enterovirus 71 inactivated vaccine [J]. Chinese Journal of Biological Products, 2015,28(12):38-41), there are also literature reports on the use of aluminum adjuvant, N, O-CMCS nanoparticle adjuvant loaded CA16 inactivated vaccine (Zhang Haoran , Jiang Li, Yang Erxia, et al. Effects of different adjuvants on the humoral immune response in mice induced by Coxsackievirus group A type 16 inactivated vaccine[J]. Drug Evaluation Research, 2020,43(5):829-834)

The common deficiency of the above-mentioned literature is that the adjuvant studied is loaded into the HFMD vaccine, which is administered by injection. Whether the same adjuvant can be applied to the soluble microneedle of the HFMD vaccine is unknown.

[0007] In addition, we know that the choice of different matrix materials will also lead to significant differences in the mechanical properties of dissolvable microneedles (Zhang Jie, Ma Fengsen, Zhan Haohui, etc., Matrix materials and composite materials used to construct dissolvable microneedles[J]. Materials Herald, 2017,31(19):129-134.), in other words, the application of different dosages of compound adjuvants in the development of EV71 vaccine soluble microneedles also has an impact on the mechanical properties and immune effects of the microneedles. Uncertainty

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