At present, the research and development of new coronal vaccine has made rapid progress. On the one hand, the public has seen the dawn, on the other hand, it has brought a lot of thinking and questions. Focusing on the concerns of relevant public opinions, the reporter of health news interviewed Wang Huaqing, chief expert of immunization program of China CDC.
■ Health News: according to media reports, the new crown vaccine is expected to be successfully developed and put on the market by the end of this year. If it comes true, it will become the fastest born vaccine in history. What are the factors behind the fast development? Is it possible to bring some hidden worries, as some people are worried about?
the so-called “fast” is mainly manifested in two aspects: first, it took less than half a year for some new coronal vaccines to enter the third phase of clinical trials from preclinical research, which is not available in history. Second, the number of new crown vaccine research and development in a short period of time is unprecedented. As of August 10, the World Health Organization (who) statistics showed that there were 28 new coronal vaccines in clinical trials and 139 vaccines in preclinical studies. Why so fast? I think there are six main factors.
first of all, there is an urgent need for epidemic control. By August 12th, novel coronavirus pneumonia cases were reported in the world over 20 million cases, with nearly 740 thousand deaths, affecting more than 200 countries or regions, which had cost a lot of medical resources worldwide and affected the development of society and economy.
secondly, all kinds of research information of Xinguan were quickly shared. As a new infectious disease, etiology, clinical science, epidemiology, vaccine science and other related research not only progress quickly, but also can be quickly shared around the world through the network, laying the foundation for rapid vaccine research and development. For example, China shared the whole genome sequence of new coronavirus with the whole world for the first time, which made the construction of recombinant vaccine of new technology gene rapidly; from the pathogenic mechanism, we quickly learned that the invasion pathway of new coronavirus was ACE2 receptor, and determined the target of vaccine research.
once again, the mature platform of new technologies enables rapid development of vaccine research and development. In addition to the traditional inactivated vaccine and live attenuated vaccine technology, this round of vaccine research and development also uses the technology of gene recombination expressing antigen in human body and the new technology of expressing antigen in human body.
fourth, the technology and process of pilot scale vaccine production are relatively mature. Therefore, the vaccine strains cultivated and constructed in the laboratory can be produced quickly and put into preclinical research and clinical trial research.
fifth, the regulatory authorities have opened up a green channel. On the basis of strict control of standards, various countries timely issued corresponding norms and opened up emergency evaluation channels, which made the clinical phase I, II and III rapidly promoted.
sixth, bilateral or multi-party cooperation is unprecedented. In order to promote the rapid, systematic and standardized development of vaccine, international organizations, relevant countries, enterprises and research institutions have carried out unprecedented cooperation.
the safety and effectiveness of the new crown vaccine are two key indicators. To this end, the World Health Organization (who) issued the third edition of the general guidelines for the target products of the new crown vaccine on April 29, this year, put forward the preferred conditions and basic conditions for the safety and effectiveness. For example, the safety conditions include that the new crown vaccine has sufficient safety and immunogenicity, based on the observed protective effect of the vaccine, it has a high return to risk ratio; the adverse reactions are only mild, and there are no serious adverse reactions. The first condition of effectiveness is that the effectiveness of protection is not less than 70%, which should also be met among the elderly, and the duration of protection should not be less than one year; the basic condition is that the effectiveness of protection is about 50%, and the duration of protection is at least 6 months.
■ Health News: at present, many new coronal vaccines with different technical routes have entered the third phase clinical stage. Please analyze the similarities and differences of these technical routes.
at present, the existing vaccine research and development technology routes are basically reflected in the research of new crown vaccines at home and abroad. There are three main technical routes for the research and development of new crown vaccines. The first is the traditional technical routes, including inactivated vaccines and live attenuated vaccines; the second is the technical routes of gene recombinant human expressing antigens in vitro, including protein subunit vaccines and virus like particle vaccines; the third is the gene recombinant human expressed antigens, which is also the latest technology route of vaccine research and development, including virus vectors Vaccine, nucleic acid vaccine.
the first type of technical route and the second type of technical route have been widely used in other vaccines. The third type of technical route vaccine, before the new outbreak, there were vaccines in human clinical trials, DNA vaccine has been used in animal disease immune prevention. The vaccine characteristics of different technical routes are different.
the advantages of inactivated vaccine are rapid research and development, mature production process, easy storage and transportation, etc.; the limitations are weak activation of immune response, multiple vaccination, high safety level of production requirements, long production cycle, and the risk of aggravating symptoms due to complex antigen components and reinfection cannot be ruled out at present.
the advantages of live attenuated vaccine are that the production process is mature, strong cellular immunity is induced, and the immune duration is long; the limitations are that the research and development cycle is long, individuals with immune disorders may become ill after vaccination, and the storage and transportation requirements are high, and there is a risk of disease caused by mutation reversion in very few cases.
protein subunit vaccine has the advantages of rapid research and development, high technology maturity, large production capacity, stable antigen, easy storage and transportation, etc.; the limitation is that mature cell expression lines are needed, antigen may be denatured, immunogenicity is not strong, and adjuvant is needed to enhance immunogenicity.
the advantages of virus like particle vaccine are large production, strong immunogenicity induced and no risk of pathogenicity; the limitation is that the research and development speed is slow, the immunization needs to be strengthened, and the technical requirements for antigen epitope screening are high.
the advantages of virus vector vaccine are high efficiency of gene delivery, can be delivered to different target organs, can produce cellular immunity and mucosal immunity, and is easy to achieve production; the limitation is that there is no fully formed supply market product at present, immunogenicity may be easily affected by pre-existing antibody of host, virus vector has potential risk, and it is not easy to repeat vaccination.
nucleic acid vaccine has the advantages of rapid research and development, strong cellular and humoral immunity, rapid generation of immunity and single expression of antigen. The requirements for industrial production are relatively simple. The limitation is that no mature vaccine for human use is put on the market, and the safety of large-scale application needs to be confirmed. DNA vaccine has the risk of integration of host genetic material, which requires high injection technology; the risk of degradation of mRNA after vaccination can produce immune tolerance, and the research and development technology requirements are high.
for a new infectious disease, its etiology, clinical science, epidemiology, vaccine science and so on are in constant understanding. Using a variety of technical routes is to select vaccines for the future, with a greater chance of success and more choices. The key indicators of vaccine are safety and effectiveness. To control a pandemic disease with vaccine, another key factor is the production and supply in a short period of time. The latest technology route can realize mass production in a short time.
■ Health News: it is generally believed that the phase III clinical trial will be the key point and touchstone for the success of the new crown vaccine. At this stage, what kind of tests will the vaccines of different technical routes undergo? Will antibody enhanced response become a stumbling block to the birth of new coronal vaccine?
no matter what kind of new crown vaccine is developed, in addition to the emergency use of the vaccine, the effectiveness and safety of the vaccine should be evaluated through three phase clinical trials. The novel coronavirus pneumonia was discovered in the process of other vaccine development before
. Many experts were worried about the development of the new crown pneumonia vaccine in ADE. Novel coronavirus pneumonia is continuing or prevalent in the three phase of clinical trials. At such a site, it is possible to assess whether ADE is taking place after the new crown vaccination. To assess the risk of disease prevention and whether the risk of ADE is acceptable.
in my opinion, there are two major difficulties in the phase III clinical trial: one is the protection effect, that is, whether the observation end point of protection effect and protection persistence can be achieved after 6 months, because the clinical trial needs enough confirmed cases; the second is safety, including whether the adverse events can be monitored enough, and whether the monitored adverse events can be scientifically judged to be related to the cause and effect of the vaccine United.
■ Health News: so, will the new coronal vaccine need to be vaccinated every year like the influenza vaccine? Are there cross protective effects between the new coronal vaccine and influenza vaccine? Is there a joint vaccine study of new coronavirus and influenza?
the virus can’t replicate itself, it needs to use the host’s cells to replicate. If the virus wants to replicate, there will be mutation. However, whether the mutation changes the characteristics of the virus needs to be monitored and studied.
influenza vaccine needs to be vaccinated every year, for one thing, the strains of influenza virus circulating each year may be different, and the other is that the protection period of the vaccine is short. Whether the novel coronavirus pneumonia vaccine is protected or whether the variation of the new crown virus is like influenza is unknown. According to the structure of viral genetic material, new coronavirus will not produce antigen drift as easily as influenza virus. As for the vaccine to be made in combination with influenza, it is uncertain at present. In addition, no cross immunization between influenza virus and new coronavirus has been found. Focus