Novel coronavirus subprotein nano vaccine and preparation method and application thereof

Abstract

The invention discloses a novel coronavirus subprotein nano vaccine and a preparation method and application thereof. The nano vaccine comprises: an organic compound self-assembled by polylactic acid, a porphyrin or a porphyrin derivative and a Co2+ ion conjugate; a novel coronavirus antigen protein; a vaccine adjuvant and lipid. According to the invention, a core of the synthesized organic compound is coated with the adjuvant, and the surface of the synthesized organic compound is efficiently loaded with the novel coronavirus antigen protein, so that a nano vaccine system for co-delivery of the novel coronavirus antigen protein and the vaccine adjuvant is implemented, and not only the immunogenicity of a novel coronavirus recombinant subprotein can be played to the greatest extent, but also the distribution condition of the nano vaccine in a living body can be traced through fluorescent molecules. In addition, the nano vaccine provided by the invention is also connected with polypeptide capable of specifically targeting antigen presenting cells, so that the nano vaccine is promoted to be massively ingested by DC cells, and the antiviral reaction is promoted. Meanwhile, the preparation method of the nano vaccine is simple and efficient, and a brand new way is provided for effective prevention of novel coronavirus infection.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a novel coronavirus subprotein nano-vaccine and its preparation method and application. Background technique [0002] Novel coronavirus pneumonia (COVID-19) is a respiratory disease caused by a new type of coronavirus (SARS-CoV-2). Its clinical manifestations range from mild flu-like symptoms to severe life-threatening pneumonia. Infectiousness and fatality. Its main structure includes spike protein (S, spike), envelope protein (E, envelope), membrane protein / matrix protein (M, membrane / matrix) and nucleocapsid protein (N, uncleocapsid). When the host is infected with the new coronavirus, the S protein will be cleaved by protease into S1 subunit and S2 subunit, and the receptor binding domain (RBD) of the S1 subunit will bind to angiotensin converting enzyme 2 (Angiotensin-converting enzyme 2) on the surface of the host cell. Converting enzyme 2, ACE2) binding, causing fever and pulm...

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Problems solved by technology

[0003] In recent years, nano-vaccine platforms dedicated to the co-delivery of antigens and adjuvants have been developed rapidly. Liposomes, albumin, and some amphiphilic block copolymers that have passed the FDA are nanocarriers used in delivery platforms in recent years. Lipids Body refers to amphiphilic phospholipid molecules as the basic material, adding cholesterol and other auxiliary materials, in water, because the hydrophobic segments of amphiphilic phospholipids are gathered together, and the hydrophilic ends are exposed to water, thus self-assembling to form the middle hydrophobic and hydrophilic ends. Bilayer structure vesicles; albumin is the most abundant protein in plasma, using albumin as a carrier for insoluble drugs to prepare drug delivery nanoparticles will make it have low biotoxicity, low immune response, biodegradability and increase half-life and other advantages, the binding force between albumin and hydrophobic small molecule drugs is mainly van der Waals force and hydrogen bond force, hydrophobic small molecule drugs are mainly loaded with the IIA region of bovine serum albumin, which can significantly improve the solubility of drugs in plasma ; Amphiphilic block copolymers also mainly rely on their own hydrophobic domains to load hydrophobic small molecule drugs through hydrophilic and hydrophobic forces, such as PLGA, due to their excellent biocompatibility, low biotoxicity and good in vivo The degradability makes it certified by the US Food and Drug Administration and officially included in the US Pharmacopoeia as a pharmaceutical excipient, and has been approved for the in vivo delivery system of various drugs, but it is difficult for the above-mentioned carriers to achieve the novel coronavirus S protein. Loading, this is due to the large molecular weight (140KD) of the new crown S protein, which has a large steric hindrance effect, and cannot be effectively loaded in a large capacity in a nanosystem; and the steric effect of the antigen of the S protein makes it only through adsorption Or water-in-oil loaded into the nanoparticle core, the above two loading methods are not only inefficient, but also easier to release, difficult to store stably

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