Since the beginning of autumn in the northern hemisphere, whether overseas or domestic, the new variant of Omicron, BF.7, has been rapidly sweeping a large number of people. This is the third-generation subtype derived from the Omicron BA.5 variant, and BF.7 is more infectious and diffusive than other types of strains, making it easy to cause widespread transmission.
More importantly, studies have shown that BF.7 may be the most immune escape variant so far.
In other words, people who were vaccinated early on are becoming more and more "naked" in the face of variants with increasingly powerful immune escape.
In the face of the new crown variant with increasing immunity escape, even the first dose of booster vaccination seems to be somewhat insufficient, and countries such as the United States, Singapore, and Israel have begun to vaccinate the population with the second dose of booster shot.
Worldwide, for the vast majority of vaccine varieties, the so-called booster shot generally refers to the third vaccination after the first two routine vaccinations. The second booster dose proposed today means a "fourth dose".
In some recent conferences held in China, some organizers have made the following regulations: if the first booster dose is more than 3 months old, participants need to receive the second booster dose before the conference.
On September 4, CanSino's inhaled adenovirus vector new crown vaccine was approved for emergency use as a booster shot.
Aside from the tongue-twisting terms of "fourth dose" or "second booster shot", it is better to understand it as the regular vaccination or revaccination of the new crown vaccine.
As for the so-called fourth dose, or the second dose of booster immunization, a number of experts believe that considering the cost and benefits of vaccination, no matter what the dosage form and technical route, there is no need to promote the general population to be vaccinated for the time being.
Some experts also said that because many people in the mainland have been vaccinated with the new crown vaccine for a long time (more than 180 days), the neutralizing antibodies in the body have dropped a lot, and cellular immunity has also declined simultaneously, according to a large number of retrospective studies, various first-generation vaccines are like this, so it is necessary to be vaccinated again to improve the level of immunity in the body.
The fourth injection, whether to hit or not, is a question
The global infection frenzy brought about by the variant BF.7 is enough to show that the protective effect of vaccines based on the original strain has been greatly reduced. Another fact is that regardless of the coronavirus vaccine, the immunity it generates in the human body will decay over time.
A study by the UK Health Security Agency showed that protection against Omicron asymptomatic infections initially reached 65-70% after a third dose of the Pfizer vaccine, but dropped to 45-50% after 10 weeks. Enhanced protection against severe disease lasted longer, with protection against severe Omicron infection at 92 percent after the third dose of the Pfizer vaccine, remaining at a high level of 83 percent after 10 weeks.
A natural question is, is it necessary to receive a fourth (additional booster) dose of the new crown vaccine to increase the protective effect of the vaccine again?
China's scientific and medical circles have been discussing this issue for months, even nearly a year. As early as December 2021, epidemiologist Zeng Guang said in public that with the emergence of new strains, the possibility of people needing a third, fourth, or even fifth booster shot is not ruled out.
On September 16, 2022, CCDC published a research article making an important judgment: vaccines are a key factor in ending the pandemic, and "it is almost certain that a second booster dose will be required at the right time".
Lu Mengji, a German-Chinese virologist and professor at the Institute of Virology at the University of Essen School of Medicine, said that the current dilemma is the lack of data to prove the effect of the fourth injection. The cycle of variant replacement of new coronavirus strains is getting shorter and shorter, and even if some data can be obtained clinically, the type of circulating strain is likely to have changed. Data from clinical trials may not reflect realistic conservation efficiency.
And phase III clinical trials need to be done in areas with epidemics, "now the immunization background of the population in each region is completely different, it makes no sense to do it abroad with epidemics, and the results are not reflected in the Chinese group, the natural infection rate is very low in the population, what role the vaccine will play, may not be representative." Lu Mengji said.
Taking the flu vaccine that is regularly updated and vaccinated every year as an example, "we can't accurately predict how protective these flu vaccines are made every year." As a rule of thumb, it is only recommended for people over the age of 60 or with underlying medical conditions. It's only after a year of flu season that you know exactly what the vaccine does. ”
Currently, the World Health Organization only recommends additional booster shots (fourth or fifth) for high-risk groups, noting in a statement: "There are some short-term benefits to additional mRNA vaccine boosters for health workers, people over 60 years of age or immunocompromised people." Limited data to support additional doses for healthy young people; Preliminary data suggest that the benefits for young people are small. ”
Due to the limited follow-up time after additional booster doses, no conclusions can be drawn about the duration of protection after vaccination. The World Health Organization based the above recommendations on research based entirely on mRNA vaccines. As far as several new crown vaccines on the domestic market are concerned, there is no experimental data to show their protective effect after additional booster vaccination.
Eight o'clock news noted that at present, many countries such as Israel, Singapore, and the United States have begun to vaccinate the population with additional booster shots.
In March 2022, when the epidemic in mainland Hong Kong was worst, the Hong Kong SAR government publicly announced that the interval between receiving the third dose of vaccine would be shortened from 6 months to 3 months, and recommended that people with weak immunity receive the fourth dose three months after the third dose.
These countries and regions made this decision mainly based on the immunity level of the population and the immune effect of the additional booster shot.
Tao Lina, a vaccine science expert, said that the fourth dose will improve the effect of preventing severe disease and death, but it is not known how long the improvement can be maintained. Even with the fourth dose, the improvement in infection prevention is still quite limited.
Older people are at high risk of infection and are more likely to become severely ill. From the current point of view, the vaccination rate of the domestic elderly vaccine booster is far from enough.
According to Beijing Daily, as of August 10, the full vaccination rate of the new crown vaccine for the elderly in mainland China was 85.6%, and the booster vaccination rate was 67.8%, lower than that of the United States (92.1%, 70.7%), Germany (91.2%, 85.9%) and Japan (92.4%, 90.3%).
Medical blogger Zhuang Shilihe pointed out to Eight Points, "Before talking about the fourth injection, it is urgent to make up the previous (vaccination rate for the elderly)." ”
Inhaled vaccines, a short-acting solution
On September 4, CanSino Biologics issued an announcement that the inhaled adenovirus vector new crown vaccine developed by the company was recommended by the National Health Commission, and the National Medical Products Administration organized the demonstration and agreed to be included in the emergency use as a booster shot. However, the vaccine still needs to go through additional administrative approval procedures before it is on the market, and the official launch time has not yet been determined.
It is worth noting that this inhaled new crown vaccine is exactly the same as CanSino's previously marketed new crown vaccine, but the injection method has changed.
CanSino Chief Scientific Officer Zhu Tao previously said in an interview that the inhaled adenovirus vector vaccine only uses 1/5 of the dose, the safety is much better than the existing intramuscular vaccine, the level of neutralizing antibodies is higher than intramuscular injection, and the neutralizing antibody can be relatively increased by more than 10 times when used to strengthen the inactivated vaccine.
CanSino Biologics has not yet announced phase III clinical trial data for this inhaled new crown vaccine.
On October 11, Wantai Biotech issued an announcement that the phase III clinical trial of the nasal spray influenza virus vector new crown pneumonia vaccine developed by it obtained key data: all subjects hospitalized and above new crown cases (WHO score of 4 points and above, including severe disease defined by the State Food and Drug Administration) were in the placebo group, and the protective efficacy of nasal spray new crown vaccine was 100%; In people with no history of immunization, the absolute protection of nasal spray vaccine over 3 months is 55%; In people with a history of immunization, the absolute protection within 6 months after using nasal spray vaccine to strengthen immunization is 82%, and the protection of people over 60 years old is not weaker than that of people aged 18~59.
Zhuang Shili and analysis, inhalation and nasal spray are equivalent to simulating viral infection, which will directly enter the upper respiratory tract and form a strong mucosal immunity in the upper respiratory tract. At the same time, he said, "In theory, mucosal immunity is difficult to measure. If you want to test antibodies to draw blood, how to do a biopsy for mucosal immunity? How high is the level of mucosal immunity, now we only have animal data, no human data. ”
According to Nature, at least nine mucosal vaccines are currently approved for use in humans, including poliovirus, flu, cholera and more. Eight of the vaccines are taken orally, and only one flu vaccine is injected with a nasal spray. The nasal spray flu vaccine is currently only available to people between the ages of 3 and 17.
Taurina analyzed that mucosal immunity is conducive to extinguishing the fire in a minimal state, and once the virus is contaminated with the respiratory tract, it can trigger mucosal immunity, which may prevent infection, "I don't know how it is, but theoretically, there is nothing wrong with this mechanism." ”
Taurina believes that "if you want to get the fourth shot, the vaccine that may be mucosal immunity should be taken out for a walk." ”
"Theoretically, the spray produces antibodies in the respiratory tract a little faster, and it may be a little better at preventing infection. There is no strong data on how this effect is. Zhang Yujiao, a tenured professor at MD Anderson Cancer Center in the United States, said. At the same time, he said that the final amount absorbed by aerosol inhalation is difficult to control.
However, a number of virologists and epidemiologists have said that inhaled vaccines have their own unique application scenarios compared with injectable vaccines.
"For example, the need for epidemic prevention and control at certain important meetings, or emergency use before the epidemic peak is expected to arrive soon." The immune protection effect brought by this vaccine may not be very long-lasting, but it can quickly improve the immune level of vaccinated people in a short period of time, and can achieve the preventive effect of reducing hospitalization and severe disease rate in the short term.
Is it time to "re-inoculate"?
According to the experience and patterns of the first two years of the new crown epidemic, every autumn and winter will be a tricky epidemic peak.
Let's take a look at the vaccination status of the new crown vaccine first. Thanks to strong action and execution, the mainland is promoting the new crown vaccination work very quickly in the world. As of October 16, a total of 3,438,277,000 doses of the new coronavirus vaccine have been reported nationwide.
However, due to the delay in the end of the new crown epidemic, the immune evasion ability and contagiousness of the variant are becoming stronger and stronger, and the first batch of people to receive the new crown vaccine may now have few neutralizing antibodies left in the body.
The once safe "vaccine" protective clothing has been slowly worn away by time, and many people can now be said to be almost "running naked" in the face of new variants.
Virology expert Chang Rongshan told Eight Point Jian Wen that a large amount of real-world data has found that no matter what type of first-generation new crown vaccine, it almost loses its protection after the 180th day of vaccination, and the situation will only get worse at 360 days (a year after the last dose).
Go back a year. According to the National Health Commission, as of October 29, 2021, more than 1.07 billion people across the country have been fully vaccinated against the new crown.
So what about the latest data? According to the National Health Commission, as of October 12, 2022, 1.27 billion people have been fully vaccinated nationwide.
In other words, in about a year, we have completed the full vaccination of nearly 200 million more people. These nearly 200 million people are relatively "new" people who have been vaccinated against the new crown, and their levels of neutralizing antibodies are relatively high.
Also during this year, we have no way of knowing how many of these 1.07 billion people in 2021 received their first booster dose. But what is certain is that a considerable part of these 1.07 billion people have reduced their neutralizing antibodies to the level of being unable to resist viral infection.
Chang Rongshan said that instead of discussing the so-called "fourth dose" or "second booster shot" of the new crown, it is better to understand it as the seasonal vaccination or revaccination of the new crown vaccine. In other words, instead of struggling with the first few shots, it is better to focus on whether the last dose of the vaccine for key groups has been too long.
Because whether it is the "first few shots", the ideal situation should be to urge the elderly to get vaccinated regularly, maintain high levels of neutralizing antibodies in the body, and help these most vulnerable people to establish or re-establish an immune barrier in response to the upcoming peak of the new crown epidemic in autumn and winter.
In the case of the already difficult situation of encouraging the elderly population to receive the new crown vaccine, it is not difficult to urge everyone to continue to receive the so-called "booster shot". The "benefits" of booster immunization are unquestionable, and public health experts and epidemiologists agree that even if it is difficult, it needs to be advanced as soon as possible.
Jin Dongyan, a virologist at the University of Hong Kong, shared a set of real-world data on Hong Kong's overall situation in 2022 for Eight Points.
In the case of a broad cause of death statistic, the overall mortality rate caused by new coronavirus pneumonia in Hong Kong in 2022 was 0.6%, and the mortality rate of unvaccinated people was 2.4%.
The mortality rate was 0.06% in those who received 2 doses of mRNA vaccine and 0.35% in those who received 2 doses of inactivated vaccine.
The mortality rate was 0.02% in the population receiving 3 doses of mRNA vaccine and 0.11% in the population receiving 3 doses of inactivated vaccine.
The mortality rate was 0.04% in the population receiving 4 doses of mRNA vaccine and 0.04% in the population receiving 4 doses of inactivated vaccine.
Thus, the benefits of 3 and 4 doses of mRNA vaccines are not significant, but 4 doses of inactivated vaccines can produce a more significant reduction in mortality than 3 doses of inactivated vaccines.
Although this set of data only shows the help of vaccination to reduce mortality, the prevention of severe disease and death are the same consideration from the perspective of epidemic prevention and control, so it can also be used as an important reference for vaccination to prevent severe disease.
Eight o'clock news previously reported that the number of critically ill patients has been rising due to the emergence of a large number of infected people.
In the peak of the severe disease in Shanghai this year, the emergency expansion of the ICU, the intensive medical forces rushing to help from all over the world, all signs show that even Omicron, which has a large number of mild cases, under China's huge population base, the challenges to the intensive medical force can not be ignored, and once a shortage of medical resources occurs, it is likely to face soaring deaths.
Chang Rongshan stressed that considering the above risks, no matter what stage of the new crown vaccine was given in the last dose, as long as it has been more than 180 days, it should be immunized as soon as possible in the near future to complete a new round of vaccination.
Regardless of the "first few shots", the ideal situation should be to urge the elderly to get vaccinated regularly, maintain high levels of neutralizing antibodies in the body, and help these most vulnerable people to establish or re-establish immune barriers in response to the upcoming peak of the new crown epidemic in the fall and winter.
Written by Xi Xiangyu and Yan Yucheng |
Chen Xin | editor
This article was first published on the WeChat public account "Eight Points Jianwen" and may not be reproduced without authorization