How are vaccines for infectious diseases developed? What is the difference between attenuated and inactivated vaccines?

Author: Wang Linghang, Chief Physician, Beijing Ditan Hospital, Capital Medical University

Reviewer: Zhang Yu, researcher at Chinese Center for Disease Control and Prevention

Infectious diseases are a type of disease caused by various pathogens that can be transmitted between people, animals, or between people and animals.

First, infectious diseases are contagious; second, there are pathogens, mainly including bacteria, viruses, fungi, protozoa, etc., which have a certain degree of epidemic and endemicity; third, immunity is produced after infection. After being infected with a certain pathogen, the body will produce a certain immunity, some of which is lifelong immunity, while some immunity may not be long-lasting.

The prevention of infectious diseases mainly involves controlling the source of infection, cutting off the transmission route, and protecting susceptible populations. Protecting susceptible populations from infection is one of the key measures for infectious disease prevention, which mainly includes two aspects: specific and nonspecific prevention. Specific prevention is mainly achieved through vaccination, which plays a vital role in controlling and even ultimately eliminating infectious diseases.

1. How are vaccines for infectious diseases developed?

During the natural infection process of infectious diseases, when the complete pathogen enters the human body, two effects will occur: one is pathogenicity, which leads to the occurrence of diseases, such as infection with respiratory infectious diseases, causing fever, cough, etc.; the other is that the immune system produces antibodies against the invading pathogens, and when infected with this pathogen again, the body will be able to exert a certain protective response.

Vaccines actually simulate the process of a pathogen infecting the human body, stimulating the immune system to target immunogenicity, causing the immune system to respond and produce antibodies, but the vaccine itself is not pathogenic. Even if it is pathogenic, the pathogenicity is within a very controllable range and will not cause damage to the human body.

Vaccine development involves complex processes, which aim to explore and prepare products that have good immunogenicity and ensure high safety. This process is often time-consuming and requires continuous passage in the laboratory to analyze the characteristics of the virus strain in order to screen out an ideal vaccine. Of course, the current construction of mRNA vaccine platforms and subunit vaccine design also provide new paths for vaccine development.

Figure 1 Original copyright image, no permission to reprint

Vaccines can use the whole pathogen, making it inactive, or use a part of the pathogen, or extract the genetic material of the pathogen, so there are many types of vaccines, including attenuated vaccines, inactivated vaccines, mRNA vaccines, and subunit vaccines. The purpose is to stimulate the body's T lymphocytes or B lymphocytes to produce immune memory and produce antibodies, so that when pathogens invade the human body, they can directly kill them or reduce their pathogenicity.

2. What is the difference between inactivated vaccines and attenuated vaccines?

Inactivated vaccines are dead vaccines. The complete pathogen has been inactivated through various methods, which means that the pathogen has completely lost its pathogenicity. However, the protein or polysaccharide components in the body can still stimulate the body to produce a certain immune response, so it is called an inactivated vaccine.

A live attenuated vaccine is one in which the pathogenicity of the pathogen becomes weaker and weaker during the generation process, but the components in its body can still be effectively recognized by the body's immune system.

Figure 2 Original copyright image, no permission to reprint

The main difference between inactivated vaccines and attenuated vaccines is safety, including some differences in immunogenicity. When used clinically, safety is considered more, and no additional health damage should be caused by the injection of the vaccine. Inactivated vaccines are safer because the pathogens have completely lost their pathogenicity and will not cause disease after entering the body. Attenuated vaccines have risks in some people. For people with impaired immune function, although the pathogenicity of the pathogen has been weakened, they may still develop the disease. For example, HIV-infected people, cancer patients, and immunosuppressed people still have certain risks when injected with attenuated vaccines.

Some vaccines are available in two types: inactivated and attenuated. If the two provide similar immune effects, it is usually more appropriate to choose the inactivated vaccine. For example, the oral polio vaccine used in the past was attenuated, but there is a potential risk of causing disease in people with impaired immune function. Therefore, the inactivated polio vaccine is now widely used to improve safety.

3. How to determine whether newly developed infectious disease vaccines are safe and effective?

The safety of the vaccine must be evaluated through clinical trials. First, we will find some subjects, mostly volunteers, to see if there are any adverse reactions after vaccination, whether there is redness, swelling, heat and pain at the injection site, whether there is fever, cough, shortness of breath, skin allergies, organ dysfunction and other systemic manifestations.

The second is effectiveness, which refers to whether antibodies are produced after vaccination, how potent the antibodies are, and how long the antibodies can exist in the body. Vaccinated and unvaccinated people are observed in the same dangerous environment to see if the probability of the vaccinated people contracting the infectious disease is significantly reduced, providing effective clinical data through observation.