September 21, 2023

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Do we have to receive the fourth dose of COVID-19 vaccine in future?

Do we have to receive the fourth dose of COVID-19 vaccine in future?


Do we have to receive the fourth dose of COVID-19 vaccine in future?

Different COVID-19 vaccines have one characteristic in common: as time passes and Delta variants sweep the world, the protective efficacy of all current vaccines has declined to varying degrees.


Recently, COVID-19s have been gradually launched in various places, but new problems have also emerged.


What kind of vaccine needs for booster shot? Is the booster shot better than the combination of vaccines or just the same? In the more distant future, will we still need to get the fourth, fifth or regular COVID-19 vaccine?



What kind of vaccines needs booster shot?

At present, the COVID-19 vaccines approved for marketing on a global scale include various technical routes such as inactivation, adenovirus, recombinant protein, and mRNA.

Under the same technical route, vaccines developed by different manufacturers may also have different inoculation doses: for example, the same adenovirus technical route, Cansino and Johnson & Johnson require only one dose, while AstraZeneca requires two doses.


Do different COVID-19 vaccines need booster shots? Whether to get a booster shot depends on the technical route or the number of inoculation doses?


In fact, the question of whether a booster dose is needed is mainly determined by the specific data on the decline in the effectiveness of each vaccine, and has little to do with technology and dosage.


This is because each of the current new coronavirus vaccines is a new type of vaccine developed by humans. Even if the technical methods are similar, the results will be different due to differences in vaccine design or production processes.


For example, Pfizer/BioNTech and Moderna have successfully launched vaccines that are the same mRNA technology line, while CureVac in Germany has a dream.


However, different COVID-19 vaccines have one characteristic in common: as time passes and Delta variants sweep the world, the protective efficacy of all current vaccines has declined to varying degrees. Mainly as follows:


1. The protective effect on hospitalization and death has decreased less;

2. After 4-6 months of vaccination, the protective power of various vaccines against symptomatic infections has decreased significantly;

3. Compared with young people, the protection effect of the elderly has been reduced more significantly. Some studies have shown that the protection of the elderly has also declined in critical illness.


Do we have to receive the fourth dose of COVID-19 vaccine in future?

Dr. Eric Topol, a member of the National Academy of Sciences in the United States, listed studies on the decline in vaccine effectiveness (Source: Twitter @Eric Topol)


However, although the characteristics of the decline are common, the magnitude of the decline may vary from vaccine to vaccine.


Pfizer’s mRNA vaccines have shown in different trials that the protection against symptomatic infections dropped from 95% to 41-84% after 4-6 months of vaccination.


There are also preliminary data that show that the effectiveness of some vaccines is slower than other vaccines. For example, the Johnson & Johnson adenovirus vaccine, a study found that although the level of neutralizing antibody at the peak is much lower than that of the mRNA vaccine, it remains relatively stable, and is equivalent to the level of the mRNA vaccine at 8 months.


What effect can the boost shot bring? In this regard, Pfizer gave further research data.


The trial included about 10,000 subjects, of which 23% were aged over 65. This percentage is very important, because according to previous research and experience, the elderly need to be strengthened.


The median interval between the second and third doses of the subjects was 11 months, and the median follow-up time after the booster dose was 2.5 months. As a result, 6 cases of symptomatic infection occurred in the booster dose group and 123 cases in the control group. Therefore, the effective rate of the boost shot to prevent symptomatic infection is 95.3%, indicating that the boost shot has restored the protection of the vaccine, even stronger, and this shot is worth a poke.


The Pfizer mRNA vaccine is currently the only new coronavirus vaccine that has the results of a boosted randomized controlled phase III trial. Although there are no phase III results for other vaccines, most of them have phase I/II results or antibody and cell response data after booster dose, including two inactivated vaccines from China SINOVAC and Sinopharm Beijing. There is no doubt that the benefits of strengthening the shot are obvious.


Do we have to receive the fourth dose of COVID-19 vaccine in future?Pfizer step-up vaccination recommendations
Source: Screenshot of Pfizer’s official website




Is it better to mix vaccines for boost shot?

So, if a booster shot is to be given, should it be the same, or is it better to mix the vaccine? If you really want to mix vaccines, what kind of combination can be more effective?


Although there are many sayings about “vaccine mixing”, according to the information released by the National Center for Disease Control and Prevention of China and the National Health Commission, mixed vaccines are not recommended. The current booster vaccination strategy adopted by China is homologous vaccination, and mixed vaccines are not recommended. It is best to vaccinate with the same technical route.


Even if the conclusion has been reached, the topic of COVID-19 vaccine smashing is still the direction of continuous exploration and research by scientists. Here, we only make professional discussions and provide some suggestions for reference only.


First of all, there are two main purposes for vaccine mixing:

1. Increase protection;

2. Reduce adverse reactions.


For research on protection, there are already a lot of data for reference.


For example, studies in the United Kingdom, Sweden, Denmark and other countries have found that the AstraZeneca vaccine followed by the mRNA vaccine can play a better protective effect than two doses of AstraZeneca. For example, a Swedish study found that the protective power of two doses of AstraZeneca was 50%, while the protective power increased to 68% after mixing the mRNA vaccine.


The most comprehensive analysis of boost shots is Chile. The Chilean government organized a “New Coronavirus Vaccine Efficacy Evaluation” study, and the results have recently been submitted to the World Health Organization.


The study found that for symptomatic COVID-19s, the protection rate 14 days after vaccination is:

  • Two doses of SINOVAC: 54%;
  • Two doses of Pfizer: 84%;
  • Two doses of AstraZeneca: 71%;
  • 28 days after one dose of CanSino: 52%.


The protection rate after the boost shot:

  • Two doses: SINOVAC + AstraZeneca: 94%;
  • Two doses:  SINOVAC + Pfizer: 95%;
  • Two doses:  SINOVAC + SINOVAC: 74%.


Do we have to receive the fourth dose of COVID-19 vaccine in future?Source: Reference 5


However, in addition to protection, we also need to consider security. On the whole, the recommendation of vaccine booster basically follows the following three guidelines:


–If the vaccine is safe and effective, it is recommended to vaccinate the same vaccine, because after all, most of the booster data in clinical trials comes from the same vaccine;


–If the side effects are relatively large after vaccination, or some people have discovered adverse reactions, consider changing to another vaccine for booster shots. For example, AstraZeneca and Johnson’s adenovirus vaccines have confirmed that the adverse reactions of thrombosis are very low. Although it is relatively rare, if there are other options, serious adverse reactions can be avoided as much as possible;


–If the protective effect of a strengthened shot is better, then a better vaccine is recommended.


One point that needs to be emphasized is that it is not that mixed vaccines are necessarily effective, but it depends on how to mix vaccines, what the preliminary research results are, and determine whether mixed vaccines are needed based on the preliminary results.

The ultimate goal of mixed vaccines is to form a vaccine combination with a wider range of immune recognition, more effective against mutations, and longer protection time, so as to provide stronger protection for humans.





Future: Do people need to get an dose every six months?


Now that the boost shots are gradually being used, we can’t help thinking whether we still need the fourth and fifth shots in the future? Is there a possibility of regular immunization, one dose every six months?


Although the long-term effect of the booster vaccination remains to be seen, some experts currently have a view. The American immunologist and chief medical adviser to the US President Anthony Fauci mentioned that he believes that three doses of vaccination may not be equivalent to two more doses. Strengthening, but more like a trilogy of complete vaccination, similar to the three shots of hepatitis B vaccine.


The six-month interval between the second and third doses allows time for memory B cells to be further improved, which can increase the diversity of antibodies, provide a broader protection for mutant viruses, and maintain a longer vaccine protection effect.


However, the new coronavirus is still undergoing mutations. Will the effectiveness of the vaccine after booster vaccination decline over time? How fast is the decline? We also need more data monitoring, and we also need to be prepared for regular immunization.


So, how often do we need a COVID-19 vaccine? An October paper in the “Nature” magazine, based on existing antibody data and model analysis, believes that the COVID-19 antibody can last for 1.5 to 2 years.


Scientists have also been studying combined vaccines against two or more respiratory viruses. For example, Novavax’s new coronavirus combined recombinant protein vaccine has shown good effects of 89.8% and 87.5% in phase III clinical trials, respectively. Moderna is also developing a combined mRNA vaccine against influenza, COVID-19, respiratory syncytial virus and human metapneumovirus.


If the development of these combination vaccines goes well, if needed, we may receive a shot of the combination vaccine before the arrival of winter every year to combat the season of high incidence of respiratory tract infections.


Dr. Offit, an American vaccine expert, pointed out that the primary role of vaccines is to prevent severe illness and death, and secondly to prevent symptomatic infections.


The data from the Phase III clinical trial of the vaccine before it is marketed represents the protection against symptomatic infections. However, after the vaccine was officially put into use, people’s understanding of the COVID-19 has been continuously deepened. A large number of asymptomatic infections have been found in large-scale nucleic acid tests. This fact also makes some people pessimistically believe that the COVID-19 vaccine does not Achieve the effect we expected.


But in fact, there has never been a vaccine in history that can prevent all asymptomatic infections. In the face of the COVID-19, we may need to adjust our expectations for vaccines back to a more reasonable level.


After all, even if the COVID-19 vaccine cannot completely guarantee that you will not be infected, it still greatly reduces the risk of severe illness and death.









Do we have to receive the fourth dose of COVID-19 vaccine?

(source:internet, reference only)

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