1. What is a bacterial vaccine?

Bacterial infectious diseases are a kind of diseases that seriously endanger human health. At present, the drugs used in clinical treatment of bacterial infectious diseases are mainly antibacterial drugs, but the abuse of antibiotics has led to a rapid increase in drug-resistant bacteria, especially multi-drug resistant bacteria. It can not effectively control infection, become a difficult problem in clinical treatment, and also bring a heavy economic burden to the society.

Bacterial vaccine can improve the resistance of susceptible populations to pathogenic bacteria, reduce the incidence of pathogenic bacteria infection, and is conducive to the control of infectious diseases. Therefore, the development of related bacterial vaccines has been a research hotspot in this field. Practice has proved that bacterial vaccines have achieved brilliant results in the development of more than a century, and have played a huge role in preventing bacterial infectious diseases. With the continuous advancement of sciences such as immunology and molecular biology, the types and compositions of bacterial vaccines have undergone great changes, and new vaccines such as component vaccines and DNA vaccines have emerged.

1. History of bacterial vaccine development

The vaccine was first introduced by Jenner at the end of the 18th century after the vaccination against vaccinia prevented the occurrence of smallpox, but no new vaccine appeared in the next 100 years. At the end of the 19th century, the French microbiologist Pasteur discovered that chickens injected with Vibrio cholerae after inoculation on artificial medium could not cause the chickens to become ill, and then attacked with wild Vibrio cholerae. The chicks, they will not have cholera. In 1881, Pasteur incubated Bacillus anthracis in the environment of 42~43 °C for 2 weeks, and then made a live attenuated anthrax vaccine. The subsequent animal experiments showed that the anthrax vaccine had protective effects on animals. This epoch-making study marks the advent of bacterial vaccines and lays the foundation for vaccinology.

From the late 19th century to the beginning of the 20th century, bacterial vaccines were the main research field of vaccinology. In addition to Pasteur, a large number of vaccination pioneers such as Emil, Kolle, Calmette, and Guerin emerged during this period. Emil immunizes the animal with diphtheria exotoxin, collects animal serum, and finds a substance that neutralizes diphtheria exotoxin, called antitoxin. Later, he detoxified the exotoxin of the diphtheria bacillus and the exotoxin of tetanus bacillus into a toxoid by formaldehyde treatment, and the toxoid as a vaccine vaccination had satisfactory results. This was the beginning of immunotherapy, for which he won the first Nobel Prize in Medicine in 1901. Kolle inactivated Vibrio cholerae in 1896 to prepare an inactivated vaccine. In 1902, this vaccine was used on a large scale in the cholera epidemic area of ​​Japan and achieved good protection. Calmette passed a 213-generation generation of Mycobacterium tuberculosis in glycerol bile potato medium for 13 years and obtained attenuated BCG in 1921. Pereira and other studies have found that inoculation of BCG to school-age children can significantly reduce Mycobacterium tuberculosis infection. In addition to the above vaccines, bacterial vaccines such as B. pertussis, Salmonella typhimurium, and Yersinia pestis were successfully prepared during this period.

1. Modern new bacterial vaccine

Since the late 20th century, related sciences such as molecular biology, immunology, and microbiology have developed rapidly. Based on this, the bacterial vaccine has developed greatly, and various modern and novel bacterial vaccines such as component vaccines and DNA vaccines have emerged, which bring R&D and production of safer, stable and protective bacterial vaccines new hope. Several modern new vaccines are introduced as follows:

(1) Component vaccine

Attenuated bacteria can be used not only as a vaccine, but also as an ideal vaccine carrier, especially in the development of genetically engineered vaccines. Attenuated bacteria can be used as a carrier to stimulate strong humoral, cellular and mucosal immunity. Classic live attenuated vaccines and inactivated vaccines are the basis of bacterial vaccine research. However, such vaccines are complex in composition and there are substances that may cause immunological side effects, and their safety and effectiveness need to be further improved.

(2) DNA vaccine

DNA vaccine is safe, easy to prepare and store, and can clone multiple target genes on the same plasmid vector to achieve a vaccine to prevent various diseases. More importantly, it simulates the exogenous activity of the body under natural conditions. The process by which a pathogenic microorganism expresses an antigen in vivo and induces an immune response. In 1989, Wolff injected the DNA plasmid into the skeletal muscle of mice and unexpectedly found that the foreign gene could be expressed in skeletal muscle cells, and the expression product could be active for up to 2 months.

1. 4. Super bacterial vaccine

Super bacteria are a general term for bacteria that are highly resistant to antibiotics. As antibiotic abuse problems become more serious, drug-resistant bacteria continue to emerge and become a global trend, and the number of deaths caused by superbugs in the United States each year far exceeds the number of deaths from HIV. In response to the prevalence of super bacteria, the development of new antibiotics or new treatments is imminent. The development cycle of new antibiotics is long, and the development of bacterial resistance is much faster than the development speed of new drugs. Vaccination plays an important role in controlling the infection and epidemic of serious pathogens in the history of human health. The specific vaccine will control the spread and infection of super bacteria from the source. The use of a Streptococcus pneumoniae conjugate vaccine has proven that vaccines can reduce the infection rate of resistant bacteria and the resistance rate of bacteria. Whether it is antibiotic-resistant bacteria or antibiotic-sensitive bacteria, vaccines can reduce their infection and reduce the spread of bacterial resistance.

The advantages and characteristics of super bacterial vaccines are mainly: (1) the use of vaccines is not affected by the existing bacterial resistance mechanisms; (2) vaccines can greatly reduce bacterial infections and reduce the use of antibiotics. The reduction in the use of antibiotics will reduce the selection pressure of antibiotic resistance, thereby delaying the emergence and spread of bacterial resistance, breaking the vicious circle of "antibiotic use - drug resistance - antibiotic abuse - pan-drug resistance". (3) The vaccine has a very strong specificity, and it only affects the specific pathogens of the human body, and does not affect the normal flora of the human body, and overcomes the side effects of the dysbacteriosis caused by the use of antibiotics.