Vaccination of “inhaled COVID-19 vaccine” has started. Why can the vaccine also be “inhaled”?

Since the end of October, many places across the country have started to start the "inhalation COVID-19 vaccine" vaccination work. On November 10, Beijing also began to make appointments for this COVID-19 vaccine. What exactly is the "inhalation" inhalation method? How is it different from the COVID-19 vaccine we have received before? And why should this "inhalation" COVID-19 vaccine be used?

This matter has to start with the new crown vaccine itself.

01

China currently

How many types of COVID-19 vaccines are available?

China’s current COVID-19 vaccines can be divided into three categories based on their technical routes[1]:

Inactivated vaccines , such as the three inactivated vaccines produced by Sinopharm Beijing, Sinopharm Wuhan, and Beijing Sinovac Biotech;

Adenovirus vector vaccine , which is adenovirus type 5 vector vaccine (Ad5-nCoV) produced by Tianjin CanSino Biologics;

The recombinant subunit vaccine is a recombinant new coronavirus protein vaccine (CHO cell) produced by Anhui Zhifei Longcom Biopharmaceutical Co., Ltd. (Zhifei Longcom).

The atomization device for the inhaled COVID-19 vaccine (left) and a simulation of the inhaled COVID-19 vaccine administration (right). Image source: cansinotech.com.cn

The "inhaled" COVID-19 vaccine is actually a type 5 adenovirus vector vaccine produced by Tianjin CanSino Biologics. This type of vaccine also needs to be "injected" (intramuscularly). The "inhaled vaccine" uses an innovative delivery method to atomize the active ingredients of the vaccine into tiny droplets, and then puts a fixed concentration into a cup and inoculates it through "oral inhalation into the respiratory tract."

Compared with the intramuscular injection version, the "inhalation" version only changes the route of administration . The formulation of the preparation is the same, and the dose required to complete the vaccination is only 20% of the intramuscular injection version.

02

Special routes of administration

There may be more unexpected effects

Will the protective effect be reduced if the dosage is reduced? The answer is: No, at least not in the short term.

In fact, the inhaled adenovirus type 5 vector vaccine has a higher level of neutralizing antibodies (Nab) in sequential vaccination. The so-called sequential vaccination is a vaccination strategy that uses vaccines of different technical routes for booster immunization according to a certain vaccination time interval and vaccination dose. One of the direct purposes of "getting" a booster shot is to stimulate the human body to produce a higher level of neutralizing antibodies. In other words, the inhaled adenovirus type 5 vector vaccine is quite effective as a booster "shot" . Why is this?

On this issue, China Business News interviewed Professor Xu Jianqing, director of the Institute of Translational Medicine at the Shanghai Public Health Clinical Center and a vaccine expert, and Professor Chen Kaixian, an academician of the Chinese Academy of Sciences[2].

The two experts said that unlike intramuscular injections, which are designed to induce humoral immune responses, the main function of aerosol inhalation booster vaccinations is to establish mucosal immunity , thereby inhibiting the infection and invasion of viruses on the respiratory mucosal surface . Therefore, inhalation vaccination can be used as a short-term and efficient way to boost immunity.

In addition, the local administration of drugs by atomization can also increase the concentration of drugs in the lungs . When administered systemically by intramuscular injection, the drug needs to pass through the pulmonary vascular barrier and circulate to the lungs to produce an effect. Therefore, to achieve a preventive or therapeutic effect, the dosage of the drug needs to be relatively increased. With atomized inhalation administration, the drug can reach the lungs through the respiratory tract without crossing the vascular barrier, so only a small amount of drug is needed to achieve the effect, which reduces both the cost of medication and the risk of side effects .

Although nebulized inhaled vaccines are uncommon, in fact, nebulized inhaled drug administration is not new. For example, common asthma medications are used in this way. In addition, many types of vaccines are currently being developed for inhaled use, such as influenza[3], quadrivalent meningococcal vaccine, and the 13-valent pneumococcal conjugate vaccine that has entered phase III clinical trials[4], all of which have attracted attention. As for the new coronavirus, many companies around the world are also researching various inhaled vaccines (in addition, oral and sublingual vaccines are also under development)[5].

In summary, the three characteristics of inhaled vaccines are very obvious:

1. Can induce body response through special immune pathways;

2. It can reach the lungs quickly and take effect quickly ;

3. Effectively reduce the dosage and medication costs . In addition, the use of inhaled vaccines can also reduce the use of needles, which can not only avoid injuries to medical staff, but also be more acceptable to the vaccine recipients.

03

Who is suitable for vaccination?

How to get vaccinated?

It should be emphasized that inhalation vaccination is suitable for boosting immunity , that is, strengthening the "needle". Therefore, at present, the "inhalation COVID-19 vaccine" is only suitable for people aged 18 and above who have completed 2 injections of inactivated vaccines (regardless of the manufacturer) or have received 1 adenovirus vector COVID-19 vaccine (intramuscular injection). People who have never received the COVID-19 vaccine or are under 18 years old cannot receive the "inhalation COVID-19 vaccine".

In actual vaccination, there are some special steps. If you are not careful, the inhalation effect may be greatly reduced.

After completing all the registrations, the vaccine recipient will be taken to an independent, relatively closed small space. The staff will use a dedicated nebulizer to nebulize the vaccine into a nebulizer cup and hand the nebulizer cup to the recipient. Each dose is 0.1 ml. The recipient's inhalation steps can be simply summarized into three steps: exhalation , inhalation , and breath holding [6]. As shown in the figure below:

The inhalation procedure for the recipient of the inhaled adenovirus type 5 vector vaccine. Image source: Reference [6]

Step 1: Avoid the atomizer cup and take a deep breath;

Step 2: Hold the nozzle of the atomizer cup in your mouth and inhale deeply until there is no mist in the cup;

Step 3: Hold your breath for at least 5 seconds.

It is worth mentioning that more vaccine varieties are of course better, but the key is that more people, especially the elderly, need to understand and accept the COVID-19 vaccine. Recently, the COVID-19 situation in my country is complicated. The virus variants spread quickly and are highly hidden. The daily increase in asymptomatic infections and mild patients may be easy to hide in the community in the early stage. Therefore, the risk of infection for the elderly is still increasing, and the elderly with chronic diseases are at high risk of severe illness and death.

Therefore, we need to call again that in order to protect the elderly, we should seize the period before the peak of various respiratory infectious diseases in winter and take our elders at home to complete the vaccination as soon as possible .

References:

[1] National Health Commission Disease Control Bureau, Chinese Center for Disease Control and Prevention. Technical Guidelines for COVID-19 Vaccination (First Edition) [EB/OL]. http://www.nhc.gov.cn/jkj/s5899tg/202104/1619f941de034452a4b9bcaf307afd79/files/d1e24d944218436d958547240af5fd07.pdf, 2021-04.

[2] Qian Tongxin. CanSino study shows that heterologous boosting of inhaled vaccine can effectively neutralize Omicron strain [EB/OL]. Yicai. https://m.yicai.com/news/101347478.html, 2022-03-14.

[3] Shi Huijie, Xi Wentao, Zhang Tianhe, et al. A review of synthetic biology and novel drug delivery routes for the prevention and treatment of influenza[J]. Education and Teaching Forum, 2020.

[4] Tu Jun. CanSino Biologics' stock price has been on a roller coaster ride on the success of its "inhaled COVID-19 vaccine". Can it reduce the infectiousness of the virus? The key to a breakthrough [EB/OL]. Blue Whale Finance. https://lanjinger.com/d/195584, 2022-11-04.

[5] Ge Hua, Jiang Liyong, Liu Shu, et al. Analysis of oral COVID-19 vaccine products and technologies[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 845-853.

[6] Inhaled COVID-19 vaccine is here! Jiangsu CDC authoritative answers questions [EB/OL]. Suzhou Municipal People's Government website. https://www.suzhou.gov.cn/szsrmzf/mszx/202211/17d506043593476a8045e86ef32a4903.shtml, 2022-11-02.

Author: Chen Mozhao

Review | Chen Gang, deputy chief physician, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

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