Shanghai started inhalation vaccination, will the new name make people more willing to fight？

Titanium media note:This article comes from WeChat WeChat official account Eight-Point News (ID: Health Insight), written by | Yan Yucheng, Xi Xiangyu, edited by | Chen Xin, published by Titanium Media with authorization.

On October 26th, the inhalation COVID-19 vaccine was officially launched in Shanghai as a booster shot. Citizens who only received two shots can choose to use the recombinant Covid-19 vaccine for inhalation (adenovirus type 5 vector) for the third shot.

On the day of vaccination in Shanghai, all districts released news that can be reserved. After visiting Jianwen at 8 o’clock, it was found that in some inoculation sites, many people called to consult the inhalation vaccine, but not many people actually vaccinated, and many people were still on the sidelines.

Among many experts interviewed by Jian Wen at 8: 00, there is a view that inhaled COVID-19 vaccine has relatively lower side effects, less pain of getting a shot, and is more friendly to the people.

There is also a view that inhalation vaccine, like other vaccines in China, can’t effectively deal with the mysterious Kerong mutant with stronger escape. "It’s just a vaccine with different technical routes, which evokes some people’s freshness."

The experts interviewed generally believe that the effect of inhaled COVID-19 vaccine can only be conservative and optimistic. Because of the lack of clinical data, it may be feasible as an emergency short-term plan with quick effect, but its long-term effect needs further observation. In addition, it is a pity that children, as the most vulnerable group in need of protection, have not been included in the vaccination plan.

Just inhale the fog in the "milk tea cup" and hold your breath for 5 seconds to complete the inoculation.

When the medical staff presses the button, an air atomizing device atomizes 0.1 ml of vaccine (1/5 of the dose of traditional intramuscular vaccine) into very small particles and pours them into an atomizing cup shaped like a "milk tea cup". The vaccinator takes a deep breath first, then holds the nozzle of the atomizing cup in his mouth, takes a deep breath until there is no fog in the cup, and then holds his breath for at least 5 seconds.

Because of the low concentration of sucrose added into the vaccine adjuvant, it is used to improve the stability of adenovirus vector. After vaccination, many people said that inhalation vaccine has a little sweetness.

This inhaled COVID-19 vaccine was produced by Kangxinuo Bio-Co., Ltd. Before that, it was only used in individual emergency situations. This time, Kangxinuo inhaled COVID-19 vaccine was launched in Shanghai to boost immunization, which is the second large-scale application at the city level since it was approved as an booster for emergency use on September 4th.

What was the vaccination situation on the first day of operation? At 8: 00, Jianwen called several inhalation COVID-19 vaccination sites, among which the staff of a community health service center in Pudong said that today (26th), 4 or 5 people were vaccinated with inhalation COVID-19 vaccine, and more than 20 people were vaccinated with other types of COVID-19 vaccine.

The staff said that there were many people who called to consult the inhalation vaccine, but not many people actually came to fight. Many people are still on the sidelines, asking mostly about the side effects of the vaccine and whether it can be used as basic immunization (the first and second injections). As it is the first day of vaccination, it is not clear whether inhalation vaccine can greatly promote the amount of booster shots.

At eight o’clock, Jianwen called another inoculation point as an vaccinator and asked if it was necessary to queue up. The staff said, "If you don’t queue up, it’s the third dose. Where are so many people?"

According to the news released by Shanghai, there are 25 inhalation COVID-19 vaccination sites in the first batch, and subsequent districts will increase or decrease the number of vaccination sites according to the actual situation. People can make an appointment to get inhaled COVID-19 vaccine on Shanghai Health Cloud. Most of these vaccination sites only provide inhalation COVID-19 vaccination service at a specific time period on one day of the week.

Among the many inhalation COVID-19 vaccination sites called for consultation, one vaccination site indicated that it was necessary to make an appointment in Health Cloud first, and only provided vaccination from 2: 00 pm to 4: 00 pm on Monday. At 8: 00, Jianwen visited three inoculation sites randomly. Two inoculation sites did not provide inhalation COVID-19 vaccination service, and the other was not at inhalation COVID-19 vaccination time.

At present, only the inhaled COVID-19 vaccine of Kangxinuo can be used for booster injection (the third injection), and the vaccination population is limited to those aged 18 and above who have completed basic immunization for 6 months.

In fact, this is not the first time that inhaled COVID-19 vaccine has been used on a large scale at the city level.

According to Xinjiang Daily, Urumqi has recently carried out inhalation COVID-19 vaccination for the key population over 18 years old who have completed intensive immunization for six months, and it has also been designated as the second dose of booster shot for specific population, which is the so-called "fourth shot".

Weibo’s account "Miao He, Xinjiang", certified as "Deputy Director of the Tourism Bureau of Bazhou, Xinjiang", said on the personal Weibo that some areas in Xinjiang have started to inoculate the fourth dose of vaccine, also using Kangxinuo’s inhalation vaccine.

In Bazhou, a month ago, the local hospital received the training of inhalation vaccine, and the staff of vaccine company introduced the advantages of inhalation vaccine to the staff of medical and health institutions and trained them in related operations.

In response to the media, Kangxinuo said: The company did provide inhaled COVID-19 vaccine to Xinjiang, and whether it was used for the fourth dose of vaccination, the company did not know.

In March 2022, the World Health Organization issued an interim statement on COVID-19 vaccine. The statement pointed out that it is hoped that the future COVID-19 vaccine will not only prevent severe illness and death, but also prevent infection and transmission, and stressed that the vaccine that can cause mucosal immunity is a more ideal choice.

According to Nature, there are about 100 mucosal COVID-19 vaccines under development around the world. About 20 of them have been clinically tested in humans, and at least 4 of them have completed or are in the process of phase III research.

As described by many experts, inhaled COVID-19 vaccine simulates the process of natural infection and can quickly activate immune cells in the nose and respiratory mucosa of the vaccinated person. According to an article by news topic in Nature on September 6th, these local cells "act as sentries of infected sites" and "they can take action faster."

On the mucosa, these immune cells will produce a kind of immunoglobulin A (IgA) called secretory immunoglobulin. If you have an impression on some news reports in the early days of COVID-19 epidemic, you may still remember that you used to distinguish whether a person had been infected with COVID-19, and the main observation was IgG and IgM antibodies in his body.

IgM means that this person may be in acute infection period, while IgG means that this person may be in late infection period or have previous infection. Similarly, these two indicators are often used to evaluate the antibody level in a person after vaccination with inactivated vaccine.

In this process, IgA is an antibody index that is not paid much attention to. It exists in both blood and mucosa, so it is difficult to evaluate its true level in human body. Moreover, because of its rapid regression, people basically don’t expect IgA to help the human body resist infection for a long time.

Today, in the case that almost all intramuscular COVID-19 vaccines are poor in anti-infection, the adenovirus vector vaccine with outstanding mucosal immune effect has become the "new favorite" and has become the current anti-epidemic vanguard.

Perhaps IgA, the once neglected "youngest son", can also become a new hope for the vaccine family?

On September 16th, the New England Journal of Medicine published a study, which provided a scientific basis for IgA antibody to prevent Omicron mutant infection.

After screening 338 medical workers who had been vaccinated with three doses of vaccine, it was found that a high level of mucosal IgA antibody could reduce the risk of Omicron infection by more than half. Dr Charlotte, the first author of the paper, said: It is not surprising that antibodies in the respiratory tract neutralize the virus locally, but these findings show for the first time that mucosal antibodies in the respiratory tract can actually prevent Omicron infection.

Many experts told 8: 00 Health News that they were conservatively optimistic about the effect of inhaled COVID-19 vaccine. If it is a short-term solution for emergency use, inhalation vaccine may have certain effect based on theory and some scientific evidence at present.

On the other hand, virologist Chang Rongshan believes that the side effects of inhalation vaccine are relatively low. Inoculators may be less prone to discomfort symptoms such as fever and fatigue, and the pain of getting a needle is less. Therefore, inhalation vaccine is more friendly than injection vaccine and may increase its appeal.

According to a grass-roots CDC worker who has experienced the workflow of Kangxinuo inhaled COVID-19 vaccine, the atomization equipment corresponding to this vaccine is relatively simple to operate, and the staff’s experience is relatively easy, which may even be lower than that of injectable vaccine. "We tried it with saline without vaccine, and there is no inhalation burden in our subjective feelings."

Behind the expectation, there are also hidden concerns.

Many experts pointed out that it may be difficult to ensure the long-term effect after vaccination because IgA antibody fades too fast and the level of neutralizing antibody evoked by inhalation vaccine in vivo is not high enough, which still needs some observation and real world data in the future.

Up to now, Kangxinuo Bio has not released the phase III clinical trial data of this inhaled COVID-19 vaccine.

In fact, the effect of mucosal immunity is difficult to measure, and there are only data from animal experiments. Tao Lina, an expert in vaccine science, said that the academic community has not reached a consensus on the quantitative determination method of mucosal immunity, involving many indicators, and how to sample is also a problem.

"Inhaled vaccines have long been used in influenza prevention, but injectable vaccines are still the mainstream because inhaled vaccines have some shortcomings." Chang Rongshan told Jian Wen at eight o’clock.

However, returning to the technical route of adenovirus vector, its immunogenicity is really not ideal — — Although it is better than inactivated vaccine, it is not as good as mRNA vaccine.

Zou Yebin, a popular science author, pointed out that the immunogenicity of inactivated vaccine is the lowest among COVID-19 vaccines used on a large scale at present, and it is only much higher than the lowest vaccine. Does it mean that the final immune protection is sufficient?

Zou Yebin said that with reference to the statistical results of neutralizing antibodies in BA.1 in Omicron, there are still many people whose neutralizing antibodies are below the detection limit after inoculation with different dosage forms of adenovirus vaccine and Zhifei booster needle. "This is BA.1, and now the mainstream Omikrongya strain may be more troublesome. “

What’s more troublesome is that COVID-19 vaccine, an adenovirus vector of Johnson & Johnson and AstraZeneca abroad, was reported earlier, which may lead to rare but serious adverse reactions — — Immune thrombotic thrombocytopenia induced by vaccine. This will lead to blood clots in the very few "unlucky" vaccinators.

However, at eight o’clock, Jian Wen noticed that there is no authoritative information to report the case of thrombosis caused by Kangxinuo’s adenovirus vector vaccine.

Kangxinuo previously issued a statement saying that the vector used is adenovirus type 5, which is different from Johnson & Johnson and AstraZeneca. At the press conference of joint prevention and control in the State Council on April 21st, 2021, National Health Commission also said that there was no report of thrombosis caused by inoculation of domestic Kangxinuo adenovirus vector COVID-19 vaccine, and the drug supervision department will continue to monitor it.

The last question is how inhalation vaccine can protect the most vulnerable people. At present, the use of this vaccine in Shanghai is restricted to people over the age of 18, but children, the elderly and people with insufficient lung capacity cannot inhale it well.

At the moment when new mutants are rampant, children are also one of the people who need protection most.

Jin Dongyan, an expert in virology at the University of Hong Kong, stressed that the experience of other overseas countries suggests that there are more and more concerns about the serious illness and death of a very small number of children infected with the mysterious Crohn, and children play an important role in the community transmission chain. However, if inhaled COVID-19 vaccine is used as the front line to prevent infection, but it does not protect children, it may become a hidden danger in the future.

According to Science and Technology Daily, Zhu Tao, chief scientific officer of Kangxinuo Biology, said that the use of inhalation vaccine can be easily mastered by children over 6 years old. Kangxinuo has plans to apply to the relevant departments for the inclusion of inhaled vaccines in the strengthening program for people aged 6-17, but the timetable has not yet been determined.