How much do you know about vaccine inactivators?

Inactivation refers to the use of physical or chemical methods to kill pathogenic microorganisms in biological products, so that pathogenic microorganisms lose the ability to infect, retain immunogenicity, and produce immune protection after use. Physical inactivation methods mainly include heat inactivation, ultraviolet inactivation and gamma-ray inactivation, and chemical inactivation methods are mainly inactivated by inactivating agents, which are the main inactivation methods in the production process of biological products. The commonly used inactivating agents of vaccines mainly include formaldehyde, β-propiolactone and so on.

Formaldehyde is the earliest and most widely used inactivator. Formaldehyde is a strong irritating carcinogen, colorless gas at room temperature, aqueous solution known as formalin, the concentration of 36% to 40%. The inactivation effect of formaldehyde is mainly reflected in its strong reducing effect, which can make the nucleic acid and shell protein of the virus denaturation and inactivation, resulting in the loss of pathogenic ability of the virus. Using formaldehyde as an inactivating agent, the process is mature and the price is low, but this method can destroy the antigenic characteristics of the virus, and the inactivation time is longer, generally need to be treated at 37~39 ℃ for more than 24h or longer, the use concentration is generally 0.1%. If the formaldehyde removal is not complete, after the injection of the vaccine, the free formaldehyde will cause the body to produce a stimulating reaction.

As a vaccine inactivator, β-propiolactone has a strong inactivation effect on the virus, which is 25 times stronger than that of formaldehyde. The inactivation mechanism is to change the nucleic acid structure of the virus by reacting with purine bases (mainly guanine), so as to achieve the purpose of inactivating the virus, without destroying the protein of the virus, and can retain the immunogenicity of the virus. In addition, β-propiolactone is easy to hydrolyze and can be completely hydrolyzed to β-hydroxypropionic acid after 2h in a water bath at 37 ℃. The product is a human fat metabolite and has no toxic effect, so there is no need to consider its residue in the vaccine. The use of β-propiolactone as an inactivating agent has the following outstanding advantages: the inactivation time is short, and the production cycle of the vaccine is shortened; it can directly act on the viral nucleic acid without destroying the protein structure, and the inactivation effect is ideal; it is easy to hydrolyze, no residue, and the hydrolysis product is harmless. β-propiolactone has been widely used in the production of various vaccines abroad. Compared with formaldehyde, beta-propiolactone is very expensive, but it has incomparable advantages over paraformaldehyde.

The effectiveness of virus inactivation is closely related to the immunogenicity of the vaccine.^®The new inactivating agent β-propiolactone used in the inactivated Japanese encephalitis vaccine (Vero cell) directly acts on the RNA of the virus, does not destroy the coat protein of the virus, is easy to hydrolyze, has no residue, and the hydrolysis product is harmless. It is an ideal inactivating agent, fully guarantees the internal quality of Chengdalibao, and better protects every vaccinator in all directions.