Varicella-herpes zoster vaccine composition as well as preparation method and application thereof

Abstract

The invention belongs to the field of vaccines, and particularly provides a varicella-herpes zoster vaccine composition as well as a preparation method and an application thereof. The vaccine composition contains varicella-herpes zoster glycoprotein E, lipid nanoparticles (LNP), a double-stranded polycytosine nucleotide fragment (Poly I: C) and a GC-rich single-stranded oligodeoxynucleotide fragment (CpG ODN), or contains gE, LNP and CpG ODN. Particles with the diameter of 20-400nm are prepared through a microfluidic device. The vaccine composition can specifically enhance humoral immune response and cellular immune response targeting the varicella-herpes zoster glycoprotein E, and can be used as a varicella vaccine without causing latent infection of vaccine strains, or as a herpes zoster vaccine. The vaccine composition has cheap and available components, thereby reducing the vaccine cost and improving vaccine yield.

Description

technical field [0001] The invention belongs to the field of vaccines, in particular to a varicella-zoster vaccine composition and its preparation method and application. Background technique [0002] Almost all children are infected with varicella-zoster virus (Varicella-ZosterVirus, VZV) before they grow up. The first infection produces chickenpox, and the virus is latent in the ganglion after the chickenpox self-healing. Cellular immunity caused by aging or other reasons A weakened response (such as HIV infection or immunosuppression) induces reactivation of the virus in the body, leading to the development of shingles. [0003] The Oka strain live attenuated vaccine developed by Japanese Michiaki Takahashi was approved by FDA in 1995 for inoculating children and adults against chickenpox (inoculation volume 1 000-5 000 PFU <plaque forming unit, plaqueforming unit> ), which are widely used all over the world. Subsequent studies have found that the Oka strain, like...

AI Technical Summary

Problems solved by technology

The key component of AS01B, QS21, is a kind that can only be obtained from South American saponins ( Quillaja saponaria ) saponins extracted by reverse high-performance liquid chromatography, currently cannot be artificially synthesized, and there are limited sources (global annual production is only 6 million copies and the main producer Chile has already Start to restrict the harvesting of related saponins), the quality control of the preparation process is difficult (the purified components are non-monomers with complex components, and the active ingredients are sensitive to temperature), and there are serious limitations such as the need to add detoxification agents due to hemolytic activity

In addition, according to the instructions of Shingrix, the adjuvant component AS01B in it needs to be temporarily mixed with the antigen before use (Bedside mix), indirectly suggesting that the stability of the liposome adjuvant system needs to be further improved when used in vaccines

The above background makes the herpes zoster subunit vaccine expensive (150-200 US dollars / injection), but the supply is still in short supply (93.3% of the vaccines were sold in the United States in 2018, and there are basically no markets outside the United States at present)

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