On the evening of December 22, Wan Bond, which had just achieved three days of three boards, received a letter of concern from the Shenzhen Stock Exchange.
The letter of concern requires that the progress of the research and development of the new crown vaccine of the new crown vector of the nasal spray recombinant Newcastle disease vector be explained, and the key links such as vaccine project establishment, preclinical research and development, clinical research, declaration and listing, approval by relevant state departments and sales, etc., fully disclose the uncertainty and related risks to the market, including but not limited to project cycle, research and development failure, vaccine approval, and the impact of production and sales on the company.
In the three trading days from December 20 to 22, WanBond achieved three days and three boards in the blessing of nasal spray new crown vaccine stocks.
On December 23, due to the impact of the Shenzhen Stock Exchange's letter of concern, Wanbond fell to a halt during the session. As of the close of trading on December 24, Wanbond rose to a limit of 13.96 yuan / share, an increase of 10.01%.
Recombinant Newcastle disease virus as vector
Is the NASAL SPRAY COVID-19 Vaccine Reliable?
According to the interview report of "Science and Technology Innovation Board Daily", the nasal spray Newcastle disease (NDV) vector new crown vaccine jointly developed by the Wanbond-Difurunsi team is a multivalent (original strain + Delta) vaccine that can stimulate the body to produce nasal-specific mucosal immunity through nasal inoculation.
Our reporter learned in many interviews that compared with the vaccines currently on the market through intramuscular injection, it is indeed insufficient to prevent upper respiratory tract virus infection, and some scientific research teams and enterprises have tried to develop nasal sprays to prevent the virus from invading the upper respiratory tract. For example, the first domestic nasal spray type influenza vaccine developed by Changchun Baike Biotechnology Co., Ltd. was listed as early as last year; the nasal spray influenza virus vector new crown vaccine jointly developed by Xiamen University, the University of Hong Kong and Beijing Wantai Bio launched clinical trials last September.
So, is it really reliable that the nasal spray new crown vaccine uses the recombinant Newcastle disease virus (NDV) as a vector? The vaccine of Wanbond's cooperation is the recombinant Newcastle disease virus, can it be used as a carrier for human nasal spraying of the new crown vaccine? How effective is it? The reporter sent an interview letter to the enterprise on the above issues, and did not receive a reply from the enterprise as of press time.
The reporter inquired about the relevant information and found that the newcastle disease virus, that is, the chicken plague virus, had previously tried to make a vector vaccine, which could prevent H5N2 avian influenza. Some insiders said that the Newcastle disease virus has also been used as an oncolytic virus before, but it is rarely used to treat people, and overall, using this virus as a new crown vaccine carrier may not have a good advantage.
Why do I need nasal sprays for COVID-19 prevention?
According to data released by the World Health Organization, more than 300 candidate COVID-19 vaccines are under development worldwide, of which 49 have been completed or are in the phase III trial stage, the vast majority of which are used by injection. So, why is nasal spraying of the COVID-19 vaccine necessary? What kind of NASAL SPRAY VACCINE IS MORE EFFECTIVE?
When talking about the necessity of developing nasal spray new crown vaccines, Xu Jianqing, distinguished professor of Fudan University, researcher of the Institute of Biomedical Research and doctoral supervisor, said in an interview with the International Finance News that the results of studies from many countries show that because the virus is constantly mutating, the protective effect of existing vaccines against new crown infections is declining.
He believes that the human immune system itself has the ability to defend against various viruses, but the activation of the human immune system requires a process of understanding the virus, and the vaccine is prevented by re-feeding the treated virus that is harmless to the human body, thereby stimulating the immune system to produce antibodies against the virus.
"The main symptom of all respiratory viral infections is the lower respiratory tract infection, which is why the new crown infection has no symptoms at the beginning, because after the new crown infection, the first 3 to 5 days are replicated in the upper respiratory tract, although there are no symptoms, but the upper respiratory virus is easy to go out, so the transmission ability is very strong."
Professor Xu analyzed, "If you want to control the new crown infection or prevent infection, you must work hard from the perspective of disease prevention, muscle vaccination can control infection, but it cannot prevent infection, including mRNA vaccines." Because in the upper respiratory tract of the human body, the virus replicates here early and spreads in the body, and it is also easier to spread to others, if only muscle vaccination is carried out, it is impossible to establish effective protection. For a COVID-19 vaccine, if you really want to prevent infection, you must establish immune protection in the upper respiratory tract, and the upper respiratory tract must establish immune protection only by nasal spray vaccine, and muscle vaccination cannot be done. ”
In addition, the human immune system has been separated since its evolution. The mucosal immune system includes the respiratory tract, the reproductive tract, and the digestive tract, which is communicated with the outside world, and the immune system that communicates with the outside world is very different from the immune system that does not communicate with the outside world.
"The reason why the mucosal immune system is isolated from other immune systems is because the mucous membrane itself is constantly in contact with external microorganisms. If you want to establish mucosal protection, you need mucosal inoculation, but simple mucosal inoculation can not form a good memory, this is because the human body has formed such a habit when it evolved. The mucous membrane is constantly in contact with external microorganisms, and if a pathogen forms a memory, it will consume all the energy it has stored. The immune system of the general mucosa is valid for about two months, so if you want to establish mucosal protection, you must have a nasal spray vaccine, but conversely, only the nasal spray vaccine can not establish a long-term memory. ”
In summary, Professor Xu Jianqing stressed, "A better way to prevent respiratory viral infections must be nasal spray vaccination plus muscle vaccination." This establishes local protection in the respiratory tract while allowing the mucous membranes to form long-term memories. If there is no muscle vaccine to continue to be vaccinated, the immune system's memory can only last for two months, and after two months, the memory gradually disappears, and the vaccine can no longer function. ”
Interview with Professor Xu Jianqing. (Photo by a reporter from the International Finance News)
Why does muscle vaccination not establish immune protection in the upper respiratory tract? For example, Professor Xu said that it can be simply compared to two interconnected rooms, and the door in the middle is open. But it is not that one room is well protected and the other room is no problem, only when one side of the room "has an accident", the "people" of the other room will rush over. That is, muscle vaccination does not establish immune protection in the upper respiratory tract, and T cells can only pass when the virus is infected, but this requires a reaction time of 48 hours.
This is why the mRNA vaccine can prevent the prevention of re-infection and control symptoms in humans. Because mRNA can advance the time when the virus enters the body, T cells will intervene quickly. If it is only through antibodies, it generally takes more than a week, and this week or more is equivalent to giving the virus a complete chance to replicate in the upper respiratory tract.
Xia Ningshao, dean of the School of Public Health of Xiamen University, also said that in the animal attack and protection experiments, it has been shown that nasal spray vaccines have a unique antiviral protection effect on new coronavirus infection in terms of rapid onset of action, broad-spectrum anti-mutation, long-term effectiveness, and emergency protection after exposure.
Nasal spray vaccines are more difficult to develop
Since nasal spraying of the new crown vaccine is very necessary, why has it not been marketed for a long time?
In this regard, Professor Xu Jianqing analyzed: "Compared with intramuscular injection of new crown vaccines, nasal spray new crown vaccines are slightly slower because of higher technical equipment requirements. At present, the vector suitable for nasal spray vaccines is preferably adenovirus vector, and the protein subunit principle is also suitable for nasal spray, but it lacks an effective adjuvant. ”
Specifically, there are the following aspects that restrict the progress of research and development of nasal spray vaccines:
First, there are limited vectors for nasal spray vaccines.
In addition to adenoviral vectors, why are many vectors not suitable for nasal spray vaccines? Professor Xu Jianqing believes that it is mainly because it has no effective adjuvant. Protein spraying on the mucous membrane does not work. This is mainly the cause of mucous membrane contact with external microorganisms. If you enter the mucosa to activate the mucosal immunity of the respiratory tract, the mucosal immune system of the respiratory tract will be "exhausted", so it is impossible to activate under normal circumstances. That's why it's so hard to find an effective mucosal adjuvant.
But he said there are now some adjuvants that are promising, such as newly developed manganese adjuvants, newly developed Cpg adjuvants and proteins of the respiratory mucosa.
Second, it is difficult to standardize the dose of vaccination.
Professor Xu Jianqing analyzed how to control the dose and the effects of the follow-up itself, it is much more difficult to standardize than intramuscular injection. In the process of spraying the nasal spray vaccine, how much of the dose itself is lost, and what is the actual dose? Which part of the process is most effective? How to use force when spraying is also very critical, is it effective to spray hard or to spray lightly? These are challenges.
Compared with intramuscular injection, the process of nasal spray, the respiratory tract varies greatly from top to bottom, and the strength of the device to control the nasal spray is very important, if the strength is small, it may enter the lower respiratory tract or enter the lungs, and it cannot induce immunity. The human respiratory tract which induces the mucosal immune response site is mainly in the upper respiratory tract, so in the process of actual use, the dose control lacks effective devices and effective monitoring of membranes and monitoring methods. Thus there are technical challenges in the development of nasal spray vaccines themselves.
Third, costs will increase.
Compared to intramuscular injections, nasal sprays also increase in cost due to the addition of devices. For example, intramuscular injection is the most traditional small needle of insulin, pre-filled into the small needle can be directly injected. The nasal spray vaccine principle also needs to be pre-filled, but the pre-filling requirements for the device are very high, the device is more complex than the original, and the corresponding cost will increase.
Although the difficulty of research and development is relatively high, at present, many pharmaceutical companies in China have begun to develop nasal spray new crown vaccines. Jointly developed by Xiamen University, the University of Hong Kong and Beijing Wantai Biology, the new crown nasal spray vaccine is a new coronavirus gene fragment inserted on the influenza virus vector to make a live virus vector vaccine to stimulate the human body to produce an immune response to the new crown virus. The advantage of its vaccine is that it has the characteristics of fast antibody production, convenient use of nasal spray administration, and rapid popularization of immunization. The most common side effects of adverse effects are runny nose or congestion, sore throat, and fever. Wantai Bio plans to carry out phase III clinical trials of nasal spray new crown vaccine in October this year.
Reporter: Hu Xinyu
Editor: Wang Liying
Editor-in-Charge: BiDandan
Cover image: Tension