Recently, the Delta mutant strain has caused epidemics one after another. Cases of "breakthrough infection" of new coronavirus pneumonia have appeared in Fujian, which has aroused public attention on vaccine booster shots. How to better play the role of vaccines has become a Hot topics such as booster shots, mixed vaccinations, sequential immunization and other keywords have entered the public consciousness.
2021.8.27
Expert advice
At a press conference held by the Joint Prevention and Control Mechanism of the State Council in Beijing on August 27, the relevant person in charge of the National Health Commission stated that strengthening the protective effect of vaccination on vaccines, from the perspective of immunogenicity See, you can get promoted. Experts suggest that vaccination can be strengthened for three types of high-risk groups: people with a high risk of infection; people who are going to overseas high-risk areas or countries; people with relatively low immune function, and people over 60 years old.
But at this stage, whether it is necessary to carry out booster vaccination for the entire population 6 months after vaccination, experts suggest that further research needs to be done, and a comprehensive judgment must be made based on the epidemic situation.
Zheng Zhongwei, leader of the Vaccine Research and Development Working Group of the Scientific Research Group and director of the Science and Technology Development Center of the National Health Commission
The Joint Prevention and Control Mechanism of the State Council mentioned the sequential immunization of vaccines with different technical routes at a press conference held in Beijing on September 7. Research. The person in charge of the National Health Commission stated that sequential immunization research must be carried out under the two principles of legal compliance and respect for science. At the expert demonstration meeting on August 2, experts clearly recommended supporting the development of sequential immunization research and pilot work.
What is the vaccine booster shot? How to give a booster shot? Can we have a mixed fight? What about sequential immunization?
Before discussing vaccine booster shots, let’s first understand the basic knowledge of vaccines and related terminology.
I am a vaccine, let’s get to know each other!
What are antibodies, antigens and pathogens
What are inactivated vaccines and viral vector vaccines
What are vaccine "protective efficacy", "protective effect" and clinical trials?
Antibody titer
Antibody titer is used to measure the minimum concentration (that is, the maximum dilution) required for a certain antibody (antibody) to recognize a specific epitope. Generally expressed as: the maximum dilution that can still produce a positive result.
simply means that the antibody titer must reach a certain level to produce an immune effect against the corresponding virus. The higher the antibody titer, the stronger the immune effect.
What do booster shots and sequential immunization mean?
The basic immunization program is a conventional fixed immunization program, using vaccines from the same manufacturer and the same technical route throughout the process. First, let’s take a look at the basic immunization procedures of the new coronavirus vaccines now available in our country.
Source: CCTV News
Generally speaking, after completing the full course of basic immunization, the probability of post-vaccination infection is still relatively low. However, no new coronavirus vaccine can prevent 100% infection. Judging from the vaccines currently on the market, its protection rate against infection ranges from 50% to 90%.
In addition, conventional vaccines often show a decrease in antibodies 6 months after vaccination. In routine vaccination, we also found that the immune effect of people with relatively low immune function and people over 60 years old after vaccination is not as good as that of people aged 18-59, but these groups are precisely the high-risk groups after infection. . Their risk of severe illness, critical illness, and death after infection is higher than that of other groups.
In the past three months or so, mutant strains such as Delta and Lambda have triggered a new round of epidemics around the world.The Delta variant, which is currently circulating in more than 130 countries and regions, has the characteristics of fast transmission, rapid replication in the body, and long conversion time. The probability of "breakthrough infection" has also increased.
The virus has upgraded, and our "weapons" must also be upgraded, so scientists are studying how to make vaccination safer and more effective and enhance the immune effect against the virus. There are booster immunization and sequential immunization.
vaccine booster shot
When injected, antibodies (a type of immunoglobulin) will be produced in the body. Antibodies have a certain half-life. When they drop to a certain level, they are not enough to protect. The vaccine can be injected again. Stimulates the body to produce and increase antibody levels. The vaccine injected at this time is called a vaccine booster shot. such as hepatitis B vaccine booster shot.
Sequential vaccination
Sequential vaccination is the interval vaccination (alternating vaccination) of different technical routes , including basic immunization sequence and booster immunization sequence.
Take the conventional two-dose COVID-19 vaccine as an example. If the first shot is an inactivated vaccine, and the second shot is an adenovirus vaccine or mRNA vaccine or any other non-inactivated vaccine, then this is " "Basic immunization sequence"; and if two doses of inactivated vaccine have been previously completed, and any other non-inactivated vaccine is used when a subsequent booster shot is required, it is called "boost immunization sequence".
When it comes to sequential immunization, many people confuse it with "vaccination mix". In fact, the two have completely different meanings. The so-called mixed use of vaccines means that vaccines produced by different manufacturers targeting the same technical route are used interchangeably on a fixed immunization schedule.
Taking the COVID-19 vaccine as an example, many people may notice that the two shots of inactivated vaccines they received are from different manufacturers. This is a mixed vaccine. Our country allows inactivated vaccines to be mixed, but new coronavirus vaccines with different technical routes cannot be mixed.
Sequential immunization applications are not uncommon
Some people ask, why should we adopt the vaccination strategy of sequential immunization?
This answer cannot be generalized. The reasons for vaccines to prevent different diseases are also different: for example, some are for vaccination safety considerations, and some are to achieve high protective efficacy and long-lasting immunity that cannot be successfully achieved by a single variety of vaccine, etc.
This is the first time for many friends to hear the term "sequential immunization". In fact, in vaccination work, sequential immunization procedures are not uncommon: such as polio vaccine, for 2-month-old and 3-month-old vaccines. Get 1 dose of inactivated polio vaccine, and 1 dose of bivalent live attenuated polio vaccine at 4 months and 4 years old. is used sequentially, which has better security and protection effect . The following takes the polio vaccine as an example to introduce the reasons for sequential immunization:
In the 1990s, the United States had basically eliminated the wild polio virus through vaccination. At that time, the live attenuated polio vaccine was used. However, it is very regrettable that because the live attenuated vaccine itself carries a certain risk of viral infection, some people develop poliomyelitis due to vaccination every year, that is, "vaccine-associated poliomyelitis" occurs.
In order to reduce the incidence of "vaccine-associated polio", the United States adopted a sequential immunization program for the first time in 1996: that is, inactivated vaccines were first used on newborns, and after a certain antiviral ability was established in an environment without infection risk, Live attenuated vaccines are then used to further enhance immune protection.
In addition to the alternate use of polio vaccines, Commonly used sequential immunization strategies at home and abroad include:
Whole-cell diphtheria-tetanus-pertussis vaccine, sequential acellular diphtheria-tetanus-pertussis vaccine, and Japanese encephalitis inactivated vaccine, sequential live attenuated vaccine Vaccines, hepatitis A inactivated vaccine followed by live attenuated vaccine, meningococcal polysaccharide vaccine followed by conjugate vaccine, and the current hot COVID-19 vaccine (such as adenovirus vector vaccine followed by mRNA vaccine), etc.
Domestic and foreign research on COVID-19 vaccine booster shots and sequential immunization
First, let’s talk about the conclusion!
01
The results of current laboratory studies on booster shots are all positive, with good safety, tolerability and immunogenicity. Moreover, the level of antibodies produced after the third dose was significantly higher than the second dose.
02
Regulatory authorities in various countries have gradually relaxed the administration of booster shots for immunocompromised people. The main disagreement at present is whether it is necessary for ordinary people to take booster shots.
03
Sequential immunization of vaccines with different technical routes can be used as a potential way to improve vaccine efficacy. Several sequential immunization studies are underway in China, that is to say, two injections of inactivated vaccines are administered, and then the third injection may be based on vaccines using other technical routes.
Picture source: Giphy
01
Israel has fully liberalized booster vaccinations
Other countries are still carefully evaluating
At present, Israel is the most active in giving booster shots in the world. On July 30, Israel began to vaccinate people over the age of 60, and later lowered the lower age limit to 12 years old. Anyone who has received two doses of the vaccine more than 5 months ago can receive a booster shot.
On August 17, 2021, local time, in Beersheba, Israel, people received the third dose of the new crown vaccine (Source: The Paper)
The United States
The Biden administration plans to start on September 20th, all Americans over the age of 18 will receive the vaccine. People are given booster shots. Regulators and academic circles believe that decisions about who needs to be vaccinated, when and at what dosage are best left to scientists.
At present, the attitude of regulators is clear. Booster shots are needed for specific people with low immune function.
On August 12, local time in the United States, the U.S. Food and Drug Administration (FDA) announced that it would expand the emergency use authorization (EUA) of the mRNA COVID-19 vaccine BNT162b2 and the COVID-19 vaccine developed by Moderna. The third dose is currently available for 12-year-olds (BNT162b2). /People aged 18 years or above (Moderna COVID-19 vaccine), solid organ transplants or those with low immunity.
02
BNT162b2The antibody titer after the third dose was
3.3 times that of the second dose
Because of the menacing new coronavirus variants, the research and approval of vaccine booster shots are accelerating.
Taking the mRNA vaccine BNT162b2 as an example, the research on booster shots is divided into three stages. As mentioned earlier, on August 12, the U.S. Food and Drug Administration (FDA) announced the expansion of the emergency use authorization (EUA) of the mRNA COVID-19 vaccine BNT162b2. This decision was based on the results of the first phase of the study. The first phase of the study mainly evaluated the safety, tolerability and immunogenicity of subjects after the third injection. The results showed good safety and strong immune response.
Subjects who received a 30-microgram booster dose 8 to 9 months after their second injection of BNT162b2 elicited higher levels of antibodies compared with antibody levels after two doses, and were resistant to both Beta and The Delta variant is equally effective. The results of the third phase of the clinical trial of
revealed that 306 subjects aged 18-55 years received a booster shot within 4.8-8 months after the second dose of BNT162b2. One month later, the neutralizing antibody titers in those who received the booster shot were 3.3 times higher than those after the second dose.
Phase 3 clinical trial data are expected to be submitted to regulatory agencies around the world soon. Based on this data, BNT162b2 will seek full approval of the new coronavirus booster shot to strengthen BNT162b2 vaccination in all people aged 16 and above.
BNT162b2 vaccine bottle (Source: Pixabay)
It can be said that the research progress and approval speed of the third shot are very fast. China has also already carried out booster shot research. On August 11, Sinopharm announced that its Sinopharm Group’s new coronavirus inactivated vaccine had completed Phase I/II clinical trials in China for people over 18 years old and 3-17 years old. The results of
show that after 3 doses of vaccination, there is no significant difference in the incidence of total adverse reactions compared with 2 doses of vaccination; and it can induce a strong antibody response. The immunity data of people over 18 years old after receiving 3 doses of the new coronavirus vaccine, All are better than the data of 2 doses of vaccination. For example, in the Phase I/II clinical trial for people aged 18-59, the GMT of the anti-COVID-19 neutralizing antibody 28 days after the second dose was 209.3; the GMT of the anti-COVID-19 neutralizing antibody 28 days after the third dose was 308.4, which is an increase. Nearly 1.5 times.
In addition to laboratory studies, booster shots also perform well in real vaccinated populations. In Israel , which is the most active in administering the third injection, according to statistics, within 10 days of the mRNA vaccine booster injection for people over 60 who were the first to receive the third injection, the vaccine provided more protection against infection than after the second injection. 4 times; 10 days later, the vaccine still provides 5-6 times the protection against severe illness and hospitalization.
03
China is studying a sequential immunization strategy, and there may be more options for the third shot.
It is worth noting that the booster shots we are talking about now are all vaccines with the same technical route. After the regular two shots, there will be a period of time. Get the third shot. The "New Coronavirus Vaccination Technical Guidelines" issued by China also recommends using the same vaccine product to complete vaccination.
At present, foreign research on mRNA vaccine booster shots is also a second shot of the vaccine with the same technical route to study its safety, tolerance and immunogenicity.
But it is not impossible for the third shot to change the technical route. Academician Gao Fu, director of the Chinese Center for Disease Control and Prevention, has publicly stated that studying the sequential immunization of vaccines with different technical routes can be used as a potential way to improve vaccine effectiveness.
A sequential immunization strategy combining different technical routes for the new coronavirus vaccine is being tried.
Zhu Fengcai, deputy director of the Jiangsu Provincial Center for Disease Control and Prevention, is leading a team to conduct sequential research on inactivated vaccines and adenovirus-vectored COVID-19 vaccines. The current reported results are very optimistic: Based on 2 shots of inactivated COVID-19 vaccine, the immune response of 1 shot of adenoviral vector COVID-19 vaccine sequentially is better than the boosted immunity of 1 shot of inactivated vaccine; moreover, the antibody levels of both There is a 7-8 times difference.
Sequential immunization of vaccines with different technical routes will produce various permutations and combinations. Currently, there are two main programs being studied in our country: inactivated vaccine + adenovirus vector vaccine/mRNA vaccine; adenovirus vector vaccine + recombinant protein vaccine /Inactivated vaccine.
In addition, not long ago, there was also a new coronavirus DNA vaccine candidate in China, which was approved to conduct clinical trials with inactivated vaccines to explore sequential immunization strategies.
Some countries that have received two doses of inactivated vaccines are also trying to change the technical route of the vaccine. In Asia, many countries using China's inactivated vaccines, such as Indonesia and Thailand, are preparing to vaccinate high-risk groups with another dose of the mRNA vaccine; Chile, Uruguay and other South American countries also have this plan. Later, more effectiveness and safety data will be disclosed.
If you are not in a high-risk group or are immunocompromised, you do not need to consider the third shot for the time being. You should finish the first two shots . As research continues to deepen, if it is time to get the third dose of the vaccine, countries will formulate corresponding policies or guidelines based on epidemic prevention and control needs and numerous research results, and we may have more and more choices.
(Information collected from: Healthy China, CCTV News, Fosun Vaccine, Vaccination)
