TNF-alpha (tumor necrosis factor-alpha) mutant protein and carrier protein CRM197 chemically coupled product and preparation method thereof

Abstract

The invention provides a protein antigen of a vaccine preparation targeting TNF-alpha (tumor necrosis factor-alpha) as well as a preparation method and an application of the protein antigen. Specifically, the protein antigen comprises recombination expression hTNF-alpha (human TNF-alpha) protein and CRM197 which are coupled through glutaraldehyde and inactivated through formaldehyde. The protein antigen almost has no TNF-alpha toxicity in the dosage of a vaccine, reserves the high immunogenicity and can stimulate mice to produce a remarkable immunoreaction targeting hTNF-alpha after being combined with an aluminum hydroxide adjuvant.

Description

technical field [0001] The invention belongs to the field of biology and medicine, and in particular relates to the preparation method and application of tumor necrosis factor alpha (TNF-alpha) vaccine with low biological activity but strong immunogenicity. The antigen prepared by the invention hardly has TNF-α toxicity, but has strong immunogenicity in mice. Background technique [0002] Tumor necrosis factor-α (TNF-α), as an important immune regulatory molecule, plays an important role in physiological and pathological processes such as cell growth, differentiation and death. TNF-α is a cytokine mainly produced by monocytes or macrophages. It can not only selectively kill certain tumor cells, but also has a variety of immune regulation functions. In recent years, studies have found that a variety of human diseases are related to high expression levels of TNF-α in the body, such as autoimmune diseases such as rheumatoid arthritis and malignant tumors. Inhibiting the funct...

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Problems solved by technology

From the experimental results, although the chemical cross-linking rate is high, it has not reached the theoretical cross-linking rate, and there are differences in the cross-linking rate of different sugars, which shows that the cross-linking rate is also related to the cross-linked product [Biophysical Journal . 2004, 86(1 Pt 1):3-9.]