动物疫苗 z-bo 2020-10-09 510

　　In 1796, Jenner developed the world's first vaccine, the smallpox vaccine, setting a precedent for humans to use vaccines to control infectious diseases. At the end of the 19th century, Pasteur, the father of vaccines, successfully developed attenuated anthrax, cholera and rabies vaccines, forming the first vaccine revolution. After more than half a century, it was a transitional period for vaccine development. People have successfully developed a variety of vaccines based on the vaccine development experience of Pasteur and others, and they have played an irreplaceable role in infectious disease control. In long-term research, people have found that the virus can grow in fertilized chicken embryos, thereby creating a safe and effective chicken embryo tissue vaccine against yellow fever, pioneering the preparation of virus vaccines. Subsequently, with the emergence and development of molecular biology technology, people began to use this technology to carry out genetic engineering vaccine research in 1962, and successfully developed hepatitis B surface antigen vaccine in 1986, which marked the beginning of the second vaccine revolution. In 1992, Tang et al. reported genetic immunization, which triggered the third vaccine revolution.

　　1. Introduction

　　The control and elimination of animal infectious diseases is not only vital to the healthy development of the breeding industry, but also significant to human health. At present, the principle of the control of animal infectious diseases is to take corresponding measures for the three links that cause epidemics, that is, to eliminate infectious diseases, cut off transmission routes and protect susceptible groups. The role of vaccines is mainly to protect susceptible groups, thereby reducing the risk of animal epidemics. It can be said that animal vaccines are the most effective means for humans to control animal diseases. However, to effectively control and even eliminate infectious diseases, vaccines alone are not enough, because the source of infection and the way of transmission are not resolved. There is a misunderstanding in the application of vaccines to control livestock and poultry diseases in my country, that is, excessive reliance on vaccines. This idea exists in a considerable number of decision-making leaders, as well as some operators and technicians. Only when we have a correct understanding of the role of vaccines in controlling and even eliminating infectious diseases in livestock and poultry can we grasp the direction of vaccine research and use vaccines correctly.

　　Most of my country's animal vaccine companies are small and highly competitive. The industry leader is China Animal Husbandry Co., Ltd. with a background of state-owned enterprises. It is the company with the highest proportion of tender seedling business (85%), and the company with the highest market share of seedlings is Ruipu Biotech (80%). Non-listed companies have posed a threat to listed companies in terms of tendering seedling bidding and market seedling sales, such as Biwei Antai, Plyco Biology, Yikang Biology, Zhongnong Weite, Qingdao Ebond, etc. The profits of animal vaccine companies are relatively high, which has attracted many investors.

　　Compared with the strict epidemic prevention system in the United States, China's animal diseases are mainly epidemic prevention. The culling system and the disease eradication system still have a long time to be standardized and implemented. Therefore, the ceiling of the industry will not appear; China's animal vaccine demand army, China's pig breeding industry is still in the initial stage of scale, and the continued increase in scale will bring about the continued growth of vaccine demand; the non-marketization of animal vaccines in China (there are government vaccines and market vaccines) system will further move towards marketization will bring industry scale Growth (the increase in government seedling prices and the liberalization of some government seedlings to the market).

　　In the future, with the continuous improvement of epidemic prevention awareness and the gradual release of market vaccines, biological products will usher in a larger market space. In 2013, the animal vaccine market was 8.38 billion yuan, and the average growth rate since 2009 was 19%. In 2015, its market size was about 12.6 billion yuan, and the national market size in 2016 was about 15.1 billion yuan, a growth rate of about 21%. According to calculations, its long-term market size will increase to about 32 billion yuan. Coupled with high barriers to foreign investment (need to establish joint ventures with domestic companies), domestic biopharmaceutical companies still have plenty of room for growth.

　　2015-2020, the domestic animal vaccine market will enter a golden period of rapid development. First, there are a huge number of economic animals that China needs to be immunized. The stock and output of major livestock such as pigs, cattle, and sheep basically maintain a growth rate of 5-10%, while aquatic products such as fish and shrimp also have vaccine requirements. Secondly, China's animal husbandry is developing towards large-scale breeding. Large-scale farming, especially high-density farming, has increased the probability of infection of livestock and poultry. Third, in order to resist the epidemic, farmers have used a lot of pesticides and antibiotics, causing excessive residues in poultry and livestock products. In the face of the "green barriers" of developed countries, the export of Chinese poultry and livestock products has been blocked.

　　Generally speaking, compared with developed countries, the scale of animal breeding in my country is still relatively low, and free-range and small-scale breeding still account for a large proportion of the animal husbandry industry. At the same time, large-scale culling models require relatively large funds, and the related frequent Sexual compensation mechanism has not yet formed in our country. Therefore, my country cannot adopt the epidemic prevention model of "culling the epidemic area as the mainstay, supplemented by vaccination and prevention" as in developed countries. It is expected that for a long time to come, the policy of "vaccination and prevention as the mainstay and culling of epidemic areas as supplement" will not change, and animal vaccines will be the main means of epidemic prevention in my country's animal husbandry. The country will continue to implement the compulsory immunization system for major diseases for a long time, and increase financial support, which will increase the demand for animal vaccines and promote the development of animal vaccine companies.

　　2. Development status of animal vaccines in my country

　　Vaccines can be divided into two categories: live vaccines and inactivated vaccines according to whether they contain live pathogens; according to their development methods and production technologies, they can be divided into conventional vaccines and new vaccines. The so-called "new vaccine" refers to vaccines developed on the basis of recombinant DNA technology and molecular biology after the 1970s, also known as recombinant vaccines or genetically engineered vaccines. Regardless of the vaccine, three elements must be considered: safety, immune efficacy and price acceptability. In addition, the ease of use of the vaccine is also a factor to be considered. The acceptability of prices among the above three elements is particularly important for animal vaccines, which is very different from human vaccines. For example, the avian flu vaccine is only a few cents per person, while the human flu vaccine costs 60 to 70 yuan per person.

　　2.1 Conventional vaccines

　　(1) Current status

　　The biggest problem with conventional live vaccines is safety. The original live vaccine is actually a wild poison. For example, in my country, the Tang Dynasty used the pus of smallpox patients to inoculate to prevent the serious outbreak of smallpox. Some countries and regions have also used the wild poison of infectious laryngotracheitis (ILT) Examples of vaccines are rare now because of poor safety. Most of the conventional live vaccines in use are artificially weakened by different methods. Because this weakening process is difficult to control, and vaccine viruses still need to multiply in animals to induce strong immunity, general live vaccines have certain residual virulence or pathogenicity. The residual virulence of the vaccine and the immune response caused are often a contradiction. From the perspective of safety, the smaller the residual virulence of the vaccine, the better, and it is best to be completely non-toxic, but such live vaccines often produce weak immunity. This is particularly evident in the live vaccine of infectious French bursal disease (IBD), which is completely attenuated and cannot induce protection in the presence of maternal antibodies.

　　On the other hand, if the residual virulence reaches a certain level, although it can produce strong immunity, it can produce clinical or subclinical diseases by itself, and in the case of IBD vaccine, it can also produce immunosuppression against other diseases. The residual virulence of the vaccine is the main cause of immune side effects. For example, the use of live infectious bronchitis (IB) and Newcastle disease (ND) vaccines in chickens causes respiratory side effects, and the use of live reproductive and respiratory syndrome (PRSR) vaccines in pigs It also produces side reactions, which are common. In addition to residual virulence, a bigger problem with attenuated live vaccines is the recombination between vaccine strains and wild strains, leading to the emergence of new strains. This is particularly prominent in live IBD vaccines. Vaccine viruses and wild viruses continue to exist in chickens at the same time, and new recombinant viruses, especially S1 gene recombination, may appear. Sometimes the vaccine virus reverses to increase the pathogenicity, such as flock A. The terminal repeats of the subgroup leukemia virus (ALV) can be activated by the MDV serotype 2 vaccine to enhance ALV replication and tumorigenesis. Although conventional live vaccines have these safety problems, they are low in cost and generally produce strong immunity. They can simultaneously induce humoral immunity, cellular immunity, local mucosal immunity, and non-specific immune responses. Therefore, they are still the protagonist of animal vaccines.

　　In addition to live vaccines, most animal vaccines are inactivated vaccines, which have the advantage of good safety. Only in a few cases, accidents occur due to incomplete inactivation. However, the cost of inactivated vaccines is more expensive than that of live vaccines, and adjuvants are needed to increase the immune response, which often requires each injection. Another important disadvantage is that it can only induce humoral immune responses. Therefore, although high levels of antibodies are present, they cannot prevent the invasion. The poison is replicated and discharged in the intestine or respiratory tract. Breeding livestock and poultry with high levels of humoral immunity produced by inactivated vaccines will seriously interfere with the active immunity of offspring. Some inactivated vaccines, especially inactivated vaccines from the entire army such as E. coli, can also cause serious side effects.

　　(2) Improvements

　　Despite these shortcomings, conventional vaccines are still the leading products of animal vaccines. Therefore, while studying new vaccines, we should not give up research on new conventional vaccines. Using conventional methods, it is still possible to develop live vaccines that have better safety and/or immune efficacy than existing vaccines. For example, in terms of live IBD vaccines, some existing vaccines cannot produce strong immunity in the presence of maternal antibodies and cannot resist super-virulent attacks, while other vaccines can produce strong immunity in the presence of maternal antibodies. Immune, and can resist super-virulent attacks, but the residual virulence is too strong, in some cases it can make chickens have strong immune suppression. Using conventional methods to develop new vaccines that can produce strong immunity under certain conditions of maternal antibodies and resist super-virulent attacks without causing significant immunosuppression in chickens has become the starting point for our work. Another example is the use of ND live vaccines to study room for improvement using conventional methods. The control of ND in my country will mainly rely on the use of vaccines at present or for a long time in the future. The key problem is that the immunized flocks have strong virulence or can still cause infections and replicate and excrete in the mucosa of the respiratory or digestive tract. Maintain spread within the group. Therefore, the study of new live vaccines requires that in addition to low virulence (ICPI≤0.4) without obvious respiratory side effects, it is also required to stimulate strong immunity, especially high levels of respiratory and digestive mucosal immunity. This vaccine will greatly reduce the level of virulent ND infection and replication in the respiratory and intestinal tracts of immunized chickens, which is beneficial to the control of ND. When discussing Marek’s Disease (MD) in chickens, Witter recently pointed out that although the use of classical virological methods to develop new vaccines is currently not favored, it may provide some promising products. He discovered in cell culture that the RMI strain is an attenuated virus that integrates the LTR sequence of reticuloendothelial hyperplasia in the MDVJM strain. It can provide protection against super virulent challenge in all strains of chickens, and is substantially more effective than the CVI988 vaccine.

　　In addition, conventional inactivated vaccines can also be improved in terms of high-efficiency immune adjuvants, enhancers and process improvement to develop high-efficiency vaccines.

　　2.2 New vaccines

　　(1) Very demand

　　As mentioned earlier, there is still room for conventional methods to study new livestock and poultry vaccines. However, in general, the traditional classical methods are used to develop live vaccines that are safer and more effective than existing vaccines. This process cannot Controlled, often random and by chance, the development of new vaccines is far less rapid than the vaccine changes in livestock and poultry groups, such as the continuous emergence of new pathogenic types and serums of IB, the prevalence of super-virulent IBD and the incidence of MD virus The virulence is getting stronger and stronger, and new and targeted vaccines that can be controlled during the research process are needed. Judging from the implementation of some infectious disease control and elimination programs and the requirements of immune monitoring, it is necessary to distinguish the immune response generated by natural infection and vaccination. Generally speaking, it is difficult for conventional vaccines to do this, but new vaccines based on DNA recombination technology and molecular biology can easily do this. Pseudorabies gene deletion vaccine is a good example.

　　For most bacterial diseases, they are live vaccines developed by conventional methods, and most of the inactivated vaccines are not effective. The control of bacterial diseases in our country mainly relies on vitamins. As antibiotics are becoming more and more serious, they not only increase the cost, but also pose an important threat to food safety. Therefore, it is urgent to use new methods to study vaccines against important bacterial diseases. There are several common requirements for new vaccines based on DNA recombination technology and molecular biology: (1) The safety should be higher than the existing conventional vaccines; (2) If the immune efficacy is not significantly higher than that of conventional vaccines, at least It is equivalent to conventional vaccines; (3) The price is roughly equal to that of conventional vaccines; (4) Some conventional vaccines can’t solve the problem, such as distinguishing natural infections and vaccine responses.

　　(2) Current status

　　There are 4 types of new vaccines that have been licensed in the world and are being studied: Type 1 is inactivated products, such as recombinant protein vaccines; Type 2 products are gene deletion vaccines made from genetically deleted pathogens; Type 3 is expression of inserted genes The carrier gene; 4 types are genetic vaccines and live DNA vaccines.

　　In the first category, there are recombinant alpha and gamma interferons, and other cytokines. Interferon-α has a significant inhibitory effect on some viral infections, while interferon-γ can enhance the expression of MHCП class molecules and increase weight gain. Subunit vaccines made from eukaryotic or prokaryotically expressed recombinant proteins also belong to this category, but few have been approved for use in the field of animal vaccines.

　　In the 2 types of products, there are gene deletion vaccines or labeled vaccines, that is, specific genes related to virulence and antibody production are deleted or changed. Serological testing can distinguish between wild virus infection and vaccine response. The most successful examples of gene deletion vaccines for livestock and poultry are pseudorabies and Salmonella enteritidis (SE) vaccines and Salmonella typhimurium vaccines, because the vaccine strains have deleted pathogenic genes and are safe to use.

　　In the three types of products, fowlpox virus, chicken Marek's disease virus (HVT and MDV type I), adenovirus, etc., and Salmonella bacteria are used as carriers. The research on vector vaccines has a history of nearly 20 years. There are many kinds of animal vaccines involved. MD vaccines and ND vaccines with fowlpox virus as carriers have been approved all over the world, but so far it has not been widely promoted and applied. not much. The reason is that the maternal antibody of the carrier or the previous immunization interferes with the immune efficacy of the recombinant vaccine. Some recombinant viruses have been cultured on cells for many times, resulting in poor replication in animals. Both aspects make the recombinant vaccines To be improved.

　　Among the four types of products, there are DNA vaccines. Its advantage is that it can induce cellular immunity and humoral immunity at the same time. However, the effectiveness of its DNA release into APC needs to be improved. It must be acceptable in terms of safety, immune effectiveness and price. Use in livestock and poultry has a long way to go.

　　(3) Improvements

　　According to the epidemic and control of animal diseases in my country, the focus of new vaccine research should be on the following types of diseases. The first is that the country needs a regional eradication program and a nationwide eradication program. According to the experience of countries around the world in implementing this plan and successfully eradicating some infectious diseases, there are stages from stopping the use of all conventional live vaccines (inactivated vaccines can be used) to stopping the use of all vaccines in this process. It will be longer. At this time, new vaccines that can replace the existing conventional live vaccines and inactivated vaccines are needed. The response of these vaccines can be distinguished from the response of wild virus infection; it should be able to supplement the lack of conventional inactivated vaccines that do not produce cellular immunity and effective local immunity. Second, the existing conventional vaccines have major shortcomings, and conventional methods are used to improve a type of disease that is difficult to overcome in the short term, such as PRRS. The third is important bacterial diseases that traditionally rely on antibiotics to control. The use of such vaccines can greatly reduce the amount of antibiotics in livestock and poultry. Fourth, for some important infectious diseases that currently have good conventional vaccines, the developed new vaccines should have 1 or 2 important characteristics that are much better than conventional vaccines, so they can be used as a supplement to conventional vaccines.

　　Special attention should be paid to the research of new animal vaccines in the future: the development of a new vaccine should be combined with the molecular epidemiological study of the pathogen in a country and region; for some diseases whose immune mechanism is not clear, such as pigs PRRS and PVC-2 infection, chicken infectious disease anemia and REV infection, etc., vaccine development must be based on the study of pathogenesis and immune mechanism; combined with pathogen genomics and proteomics research.

　　In the 21st century, human beings have entered the post-genome era, and it is not too long to determine the complete genetic sequences of most important infectious pathogens. At present, most viral pathogens have complete genetic sequences. In recent years, the complete genome of pathogenic bacteria has been completed every year. Group sequences are more than 20 kinds. Some new technology platforms based on the entire genome sequence of pathogens, such as reverse genetic technology of RNA viruses, and technology of producing infectious viruses by subgenome cosmid fragments of DNA viruses, provide a broader space for the development of a new generation of virus vaccines. Reverse vaccinology, developed on the basis of bacterial genomics and proteomics, uses large-scale, high-throughput, automated, and computer analysis research methods to screen a large number of bacteria from the whole genome level in a short period of time. Candidate antigens for protective immune response, and the completion of cloning, expression and purification will undoubtedly open up a new way for the development of new vaccines for some complex pathogens, especially bacterial pathogens. The development of vaccines for subgroup B Neisseria meningitidis is a success. example. But no matter what kind of new vaccine, in addition to safety, improving the immune efficacy in commercial animal groups is still a difficulty that needs to be overcome.

　　3. The impact of my country's animal vaccine policy

　　(1) The animal vaccine industry is significantly regulated by policies

　　Animal vaccines are mainly divided into economic animal products (pigs, chickens, cattle, sheep, etc.) and pet products. Most of the pet products use imported vaccines. The market share of domestic enterprises is extremely low, and import substitution still takes time, so Generally speaking, animal vaccines only refer to economic animal products. Animal vaccines are a policy-sensitive industry. On the one hand, the breeding industry itself is subject to policy regulation. For example, in recent years, environmental protection pressures have led to a sharp decline in pig stocks, which indirectly affects the demand for animal vaccines. On the other hand, the production of animal vaccines involves biosecurity. It is also strictly controlled by the Ministry of Agriculture, including applications for designated production qualifications, new veterinary drug certificates, and production document numbers, all requiring strict approval. Especially in terms of compulsory immunization vaccines, it is precisely because of policy restrictions that manufacturers of foot-and-mouth disease and highly pathogenic avian influenza have been kept in the single digits. In addition, the advancement of mandatory immunization policies in history has also led to explosive growth in the vaccine market.

　　(2) Industry policy review

　　Industry programmatic document "National Medium and Long-term Animal Disease Control Plan (2012-2020)"

　　On May 2, 2012, the National Medium and Long-term Animal Disease Prevention and Control Plan (2012-2020) was reviewed and approved by the executive meeting of the State Council and promulgated and implemented by the General Office of the State Council. This is the first comprehensive plan to guide the prevention and control of animal diseases nationwide since the founding of New China, marking that the prevention and control of animal diseases has entered a new stage of planning and scientific prevention and control.

　　According to the plan, my country has 29 types of animal diseases that are prioritized for prevention and control. Among them, there are 5 domestic first-class animal diseases, including foot-and-mouth disease (type A, Asian type I, and type O), highly pathogenic avian influenza, Highly pathogenic swine blue ear disease, swine fever, Newcastle disease.

　　Animal diseases with priority control and key prevention

　　The plan proposes that by 2020, 16 domestic animal diseases that are prioritized for prevention and control, including foot-and-mouth disease and highly pathogenic avian influenza, will meet the assessment standards set by the plan, and the incidence of pigs, poultry, cattle, and sheep will drop to 5%, 6%, Below 4%, 3%, animal morbidity, mortality and public health risks are significantly reduced. The risk of introduction and spread of 13 key foreign animal diseases, including bovine spongiform encephalopathy and African swine fever, has been effectively reduced, and the ability to prevent and handle foreign animal diseases has been significantly improved.

　　The "two in and two out" policy will be implemented in 2017

　　On July 21, 2016, the Ministry of Agriculture and the Ministry of Finance issued the "Notice on Adjusting and Improving Support Policies for the Prevention and Control of Animal Diseases". The main contents include: 1) The state continues to impose compulsory measures on foot-and-mouth disease, highly pathogenic avian influenza, and petit ruminants. Immunization and compulsory culling; 2) Bringing brucellosis into the scope of compulsory immunization in provinces (type 1 areas) where brucellosis is severely affected, and expanding the range of livestock species for brucellosis and tuberculosis compulsory culling from dairy cows to all cattle and sheep; 3 1) Equilibrium and horse-borne poverty shall be included in the scope of compulsory culling; 4) Hydatid disease will be included in the scope of compulsory immunization and compulsory culling in the provinces severely affected by hydatid disease; 5) For swine fever and highly pathogenic pig blue ear The national compulsory immunization policy will not be implemented for the time being. The country will formulate guidelines for the prevention and treatment of swine fever and highly pathogenic blue ear disease, and various localities will carry out prevention and control work according to actual conditions; 6) The plan will be implemented from January 1, 2017.

　　The 13th Five-Year Plan for veterinary health undertakings is released, and the supervision of the whole chain will be strengthened

　　Development goals: The plan points out that by 2020, the concentration and competitiveness of the veterinary drug industry will be further improved, with medium-sized and above production enterprises accounting for more than 70%, and capacity utilization rate increasing by more than 10%. At the end of the 13th Five-Year Plan, the qualified rate of veterinary drug product quality random inspections has stabilized at over 95%. The slaughter volume of hog slaughter companies above designated size accounted for more than 80%, the slaughter rate of live pigs dropped by more than 10%, and the “small, scattered and chaotic” situation of hog slaughterhouses was basically improved.

　　Key tasks: Planned control and purification of key diseases: foot-and-mouth disease and highly pathogenic avian influenza continue to implement compulsory immunization. Intensify regional management of brucellosis, and promote the monitoring and purification of farms and key breeding areas. The prevention and treatment of tuberculosis in dairy cows is a combination of risk assessment, mobile control and quarantine and culling. Rabies focuses on strengthening immunization and epidemic surveillance, and coordinating and promoting canine registration management. Schistosomiasis focuses on the control of livestock infection sources, and implements comprehensive agricultural management. Implement preventive measures such as deworming and immunization for echinococcosis, and strengthen quarantine and slaughter management. Highly pathogenic swine blue-ear disease, swine fever, Newcastle disease, salmonellosis, avian leukemia, swine pseudorabies and porcine reproductive and respiratory syndrome, strengthen the source monitoring and purification. Maintain the nationwide epidemic-free status of equine meliosis, and strive to eliminate equine infectious anemia nationwide by 2020. In-depth implementation of the "National Pediatric Ruminant Disease Elimination Plan (2016-2020)", and strive to 2020, with the exception of the land border counties (group farms) adjacent to the Pestle Ruminant epidemic country or the immune isolation zone within 30 kilometers along the border , The rest of the country has reached the standards of non-immune-free areas. Preventing the risk of imported animal diseases: adhere to the combination of dredging and blocking, focusing on preventing the African swine fever, bovine spongiform encephalopathy and other foreign animal diseases identified in the National Medium and Long-term Animal Disease Prevention and Control Plan (2012-2020).

　　Main changes: The "13th Five-Year Plan" proposes to build an information system for the entire chain of veterinary health supervision services, emphasizing the supervision of the entire chain from breeding to slaughter, especially the supervision of the slaughter industry.

　　(3) The impact of policies on animal vaccine innovation

　　As far as animal vaccines are concerned, conventional vaccines are still the mainstay in the world, and this is also true in my country. Conventional vaccines will still dominate the market for a long time to come. This is because: ①The development cycle of genetic engineering vaccines is long, and the safety evaluation requirements are stricter; ②There are not many vaccines whose immune efficacy reaches or exceeds that of conventional vaccines. Currently, there are only gene deletion vaccines such as pseudorabies and salmonella and E. coli vaccines for piglet dysentery. A few; ③There are many genetically engineered vaccines under development, their production costs are high, and the acceptability of prices is a big problem.

　　Based on the above situation, the research of livestock and poultry vaccines in my country should have two approaches: one is conventional vaccine research, using new conventional vaccines to supplement or replace existing conventional vaccines; the second is to increase the research and development of new vaccines and develop new vaccines that can be used High-efficiency vaccines for livestock and poultry infectious disease control and elimination programs. Three aspects of the development of livestock and poultry vaccines will be discussed below: ①The main shortcomings of conventional vaccines and the room for research and improvement; ②The demand for new vaccines and the new vaccines that have been used and are under research; ③The future development direction of new vaccines.

　　With the advancement of vaccine research technology in my country and the upgrading of vaccine R&D and production equipment, the level of vaccine production and inspection technology in my country has been greatly improved, and the quality of products has been significantly improved. The quality of many products is higher than that of similar foreign products. The speed of product upgrading and the price are accelerated. There has been an increase, and the profit margin has also increased. Traditional inactivated vaccines, attenuated vaccines, bioreactors, high-density fermentation, immune adjuvants, heat-resistant freeze-dried protective agents and other technological advancements have accelerated, product quality has been accelerated, conventional poultry vaccines have basically replaced imported vaccines, and swine vaccines It is also rapidly replacing imported vaccines. Genetically engineered high-tech vaccines such as genetically engineered deletion vaccines, synthetic peptide vaccines, subunit vaccines, and live vector vaccines have entered the vaccine market. DNA vaccines and genetically modified plant vaccines will also enter the vaccine market. I believe that these high-tech vaccines will continue to replace The entry of traditional animal vaccines into the market will definitely promote the prosperity and development of the animal vaccine market.

　　As the market has higher and higher requirements for product quality, the cancellation of government bidding and the liberalization of market seedling sales will be the general trend, and the price increase brought about by the improvement of quality will promote the expansion of the industry.

　　The large-scale animal husbandry industry has increasingly stringent requirements for vaccine safety, protection effectiveness, quality, and ease of use of vaccines. In response to the needs of the industry, the research and development of the animal vaccine industry in recent years has focused on new adjuvants, antigen purification, high-throughput screening of cell lines or virus strains, and suspension culture.

　　Vaccines are biological products that are extremely sensitive to the external environment. If they are not stored in a suitable temperature range, their effectiveness will decrease or even be completely destroyed. Especially in rural areas with weak infrastructure-these areas are usually very in need of animal vaccines, and vaccines are often spoiled and ineffective. With the development and emphasis of various provinces on the cold chain system in recent years, the above situation has been well improved. The cold chain is the whole process of maintaining the quality of vaccines in the best condition. The initial link of the cold chain is the vaccine manufacturer. After specific links such as transportation, storage, and management, the end of the vaccination is completed. In all links of the cold chain, vaccines must always be kept strictly within a narrow allowable temperature range to avoid potential safety hazards in vaccination. The improvement of the cold chain system will expand the market for animal vaccines in more regions.

　　At present, most of the animal vaccine companies in my country have weak research and development capabilities, with little investment in new product development, lack of strong technical support for new product development, and lack of independent innovation capabilities. Only a few companies have the ability to develop new vaccines. According to statistics from the China Veterinary Medicine Association, the total R&D investment in the industry in 2010 was 445 million yuan, and the average R&D investment of each animal vaccine company was only a few million yuan. Compared with foreign companies' R&D investment of hundreds of millions of dollars, the gap is very obvious. The industry's overall weak R&D capability and low R&D investment have affected the development of the domestic animal vaccine industry to a certain extent.

　　The animal vaccine industry is an industry with knowledge and technology products as its core competitiveness. I believe that with the deepening of the government’s reform of streamlining administration and delegating powers, and the continuous improvement of government bidding and procurement policies, the animal vaccine industry will surely return to its true colors, and knowledge and technology products will surely become The core competitiveness of animal vaccine companies. Innovation-driven, brand-driven, and market-driven development have become new driving forces for enterprise development. It is a development trend that the market share of vaccines will exceed the share of government procurement of vaccines. Reform drives innovation, and innovation drives development. Innovation is an inexhaustible driving force for the development of animal vaccine companies and industries. Since animal vaccines account for a small proportion of the production costs of modern-scale breeding enterprises, as a precaution, modern-scale breeding enterprises have a strong demand for high-quality animal vaccines. If an animal vaccine company wants to meet the needs of the production market and achieve sustainable development, it must have a powerful "engine". This "engine" is the company's own R&D organization. The R&D organization needs to have the actual combat capability to solve practical problems and also need to have With foresight and foresight, it can put forward strategic research topics and development directions. Therefore, future animal vaccine companies need to strengthen the introduction and training of talents in their own research institutions, establish and improve their own research institutions, give full play to their resource advantages, actively cooperate with domestic and foreign research and development institutions to innovate, and continue to develop new animal vaccine products. Vaccine companies give confidence to the domestic aquaculture industry. As the research and development of a new animal vaccine product costs tens of millions or even hundreds of millions of yuan, a company is often unbearable. Therefore, voluntary combination research and development consortia between companies and companies, vaccine research institutes and companies, and universities and companies are increasing. They closely follow the forefront of international science and technology and face the demand of the production market. They have developed new animal vaccine products one after another.

It is not enough to have a good engine. Although most animal vaccine manufacturers are currently undergoing the transformation of high-end vaccines in the market, not all companies can produce high-quality vaccines. Although the production principle is simple, the production process is complicated. In addition, a high level of production management, quality control procedures, and a strong sense of responsibility are required. Details often determine success or failure. This is also the core reason why the quality of domestic vaccines has long been difficult to match the international giants. The stable quality of existing production products is the basis of market stability. The design of product quality, product control, and product process innovation in this link all require the company to attach great importance to the on-the-job training of key production technicians and the cultivation of corporate loyalty. Important, this process is a long-term process for the company. The brand and credibility of the company are slowly cultivated, not overnight, but the company must also have a certain emergency response capability and prepare a series of emergency prevention in case of emergency.