covid-19 war “epidemic” has entered its third year, the global epidemic is still spreading, and many countries in the world are facing severe challenges in epidemic prevention and control
So far, the cumulative number of confirmed cases of covid-19 pneumonia in the world has exceeded 500 million, which is only three months from the 300 million cases in early January.
In addition, from March 1 to April 18, China’s 31 provinces (autonomous regions and municipalities directly under the central government) and Xinjiang production and Construction Corps reported a total of 497214 cases of local infection, affecting all provinces except Tibet Autonomous Region.
Under the continuous variation and rampant of covid-19 virus, the global pandemic has not yet ushered in a “turning point”. In this situation, as the first line of defense against covid-19 virus, vaccine is still the most effective means for mankind to deal with the crisis.
According to the data of the National Health Commission, as of April 23, 2022, 31 provinces (autonomous regions and municipalities directly under the central government) and Xinjiang production and Construction Corps had reported 3329766 million doses of covid-19 virus vaccine. In addition, according to the statistics of our world in data of Oxford University, as of 16:00 on April 21, London time (23:00 on April 21, Beijing time), the world has reported 11.49 billion doses of covid-19 virus vaccine, and 65% of the world’s population has been vaccinated with at least one dose of covid-19 vaccine.
however, now the completion of the whole course vaccination is not enough to build a strong immune barrier, and vaccination booster has become one of the most effective and feasible ways to effectively reduce the severe and mortality of covid-19 globally at this stage 4 on April 21, at the 2022 annual meeting of Boao Forum for Asia, Zheng Zhongwei, leader of the working group of vaccine research and development of the joint prevention and control mechanism of the State Council, also pointed out that with the evolution of the epidemic, more than two years of practice has proved that two doses are not enough to achieve the best protection effect, and the third dose is imperative.
As early as last October, China launched covid-19 vaccine booster vaccination (homologous booster immunization), and then in February this year, the National Health Commission began to deploy sequential booster immunization (commonly known as “mixed vaccination”).
For the target population over 18 years old who has been vaccinated with inactivated vaccines of Sinopharm Zhongsheng Beijing company, Wuhan company and Beijing Kexing company, as well as adenovirus vector vaccine of Tianjin Cansino Biologics Inc(688185) company for 6 months, one dose of secondary homologous booster immunization can be carried out, that is, the original vaccine can be used for booster immunization. After the implementation of the sequential booster immunization strategy, the target population who has completed the whole process of vaccination with the above three inactivated vaccines can also choose the recombinant protein vaccine of zhifeilongke horse or Cansino Biologics Inc(688185) of adenovirus vector vaccine for sequential booster immunization.
According to the National Health Commission, as of April 18, China had reported 3317463 billion doses of covid-19 vaccine, with a total number of 1.282 billion people vaccinated, and 1.246769 billion people had been vaccinated in the whole process. The number of people covered and the number of people vaccinated in the whole process accounted for 90.94% and 88.43% of the total population respectively. 732659 million people were vaccinated, of which 25.426 million were vaccinated sequentially. The number of vaccinations for the elderly over 60 years old reached 225521 million, and 213938 million people were vaccinated in the whole process. The number of people covered and the number of people vaccinated in the whole process accounted for 85.41% and 81.03% of the elderly population respectively. Immunization campaigns have been strengthened for 154874 million people.
from the data, it can be seen that the covid-19 vaccination rate of the elderly in China is generally low. This also brings development opportunities for follow-up Chinese vaccine enterprises, especially those approved to strengthen the vaccine in sequence
However, with the gradual end of the covid-19 vaccine competition in the first half, despite the huge demand for vaccination in China, most of its covid-19 vaccines are still in the clinical trial stage due to the late entry of the “latecomers”, and the situation of the sequential strengthening competition in the second half is still unknown.
1. Severe and complex epidemic situation outside China
At present, the global epidemic situation is still grim. A new round of epidemic attacks many countries, and new confirmed cases continue to be found in various countries.
According to the real-time statistics of worldometer, as of around 6:30 on April 22, 2022 Beijing time, 82532355 cases of covid-19 pneumonia and 1017449 deaths have been confirmed in the United States; Compared with the data at about 6:30 the previous day, there were 91023 new confirmed cases and 1108 new deaths in the United States.
In addition, according to public reports, since April, some U.S. government officials and members of Congress have been diagnosed one after another. On April 11 local time, representative Rashida tlaib of Michigan announced that his covid-19 pneumonia test result was positive. After diagnosis, he is currently being isolated at home. On April 10, the New York City Government issued a statement saying that New York Mayor Adams tested positive for covid-19 virus that day. At present, he has no other symptoms, has been isolated and will cancel the public activities. On April 9, US Secretary of agriculture Tom Vilsack said that his covid-19 virus test result was positive, becoming another US secretary who confirmed covid-19. On April 7, House Speaker Nancy Pelosi tested positive for covid-19 virus. On April 6, US Secretary of Commerce Raymond and attorney general garland confirmed covid-19 virus infection successively.
Xinhua news agency said in its report on April 11 that recently, the covid-19 epidemic in the United States seems to be in a platform stage, but epidemiologists said that factors such as incomplete epidemic data statistics may seriously underestimate indicators such as the daily increase in the number of confirmed cases in the United States, so that the upward trend of the epidemic is “covered”. With the advent of Easter, spring break and other holidays in the United States, there are more parties, the virus may accelerate the spread, and the epidemic in the United States may rise again.
On April 21 local time, the latest statistics released by the Italian Ministry of health showed that in the past 24 hours, 75020 cases of covid-19 pneumonia were newly confirmed in the country, with a total of 15934437 cases; There were 166 new deaths, with a total of 162264 deaths; 59916 cases were newly cured, with a total of 14549360 cases cured; There are 1222813 confirmed cases.
Xinhua reported that on March 31, Italy ended the state of emergency caused by covid-19 epidemic and relaxed epidemic prevention measures from April 1.
People no longer need to show covid-19 “green pass” when entering banks, shops, post offices and outdoor areas of restaurants, or taking public transport in the city.
According to the data released by the French public health department on April 21 local time, as of the afternoon of that day, the cumulative confirmed cases of covid-19 pneumonia in France reached 28076047, with 104007 new cases in 24 hours. The cumulative number of deaths reached 144799, with 167 new cases in 24 hours. French health minister Olivier Welland said in an interview with the media on April 7 that France had crossed the peak of the rebound of the epidemic. However, the French Public Health Bureau later called for caution, saying that covid-19 virus is still spreading, and it can not be said that the peak rebound of the epidemic has passed.
In addition, according to the notification of the central epidemic prevention headquarters of South Korea, as of 0:00 on April 21, there were 90867 confirmed cases of covid-19 virus infection in South Korea compared with 0:00 the previous day, 20452 confirmed cases in a single day and 147 new deaths; 16674045 cases were diagnosed and 21667 cases died. The average mortality rate was 0.13%.
In addition, according to South Korean media reports, the South Korean disease control department said on April 19 that South Korea found two cases of infection with covid-19 recombinant strain Xe and one case of infection with XM for the first time. The South Korean disease control department said that the who classified Xe and XM as Omicron like strains, with characteristics similar to the original strain ba 1 not much different. In view of the lack of information on its transmissibility and severe disease rate, the epidemic prevention department will strengthen the monitoring of mutant strains.
South Korea’s disease control department said on April 12 that China has found the first confirmed case of covid-19 recombinant strain XL infection and is conducting epidemiological investigation. It is reported that XL strain is one of the 17 recombinant strains (XA ~ XS) found so far, which is composed of the original strain Ba of “Omicron” 1 and subtype ba 2 recombined. However, there is no information on the transmission characteristics of XL strain, which was previously found only in the UK.
According to overseas network news, South Korean Prime Minister Kim Fu him announced on April 15 that from April 18, the restrictions on maintaining social distance will be completely lifted, and the epidemic prevention measures of compulsory wearing masks indoors will still be retained. It is understood that the epidemic prevention measures to maintain social distance in the country have been implemented since March 2020, and it has been two years and another month. In addition, since April 18, private gatherings and large-scale events and gatherings in South Korea are no longer limited by the number of people, high-risk business places can operate 24 hours, and religious facilities are no longer limited. This means that South Korea chose to “lie flat” against the background of the severe situation of epidemic prevention and control.
According to the latest statistics released by the Robert Koch Institute, the German federal agency for Disease Control and prevention, as of 0:00 local time on April 21, the cumulative confirmed cases of covid-19 pneumonia in Germany reached 23844536, an increase of 186325 cases compared with the previous day; There were 133632 deaths, 324 more than the previous day.
According to China Central Television News, Agence France Presse reported on April 21 that a German finance ministry official said that German finance minister Christian Lindner, who was attending the spring meeting of the International Monetary Fund and the world bank in Washington, D.C., tested positive for covid-19 virus. Lindner confirmed the news on social media that day.
On April 8 local time, German health minister lautbach said that after legislators rejected the proposed fourth dose of vaccine, Germany may need to re implement the requirement of wearing masks in public this autumn. For this reason, Bach sent the wrong signal to reduce the burden of compulsory quarantine. But the pandemic is not over. “We still have more than 300 deaths every day,” lautbach stressed at a news conference.
at present, China is also suffering from the impact of a new round of epidemic, with sporadic local epidemics throughout the country, and the number of covid-19 infection cases per day is still high
At the press conference of the joint prevention and control mechanism of the State Council on April 19, according to Wu Liangyou, deputy director of the Bureau of disease control of the National Health Commission: from March 1 to April 18, 31 provinces (autonomous regions and municipalities directly under the central government) and Xinjiang production and Construction Corps reported a total of 497214 cases of local infection, affecting all provinces except Tibet Autonomous Region. Recently, the national epidemic situation has gradually stabilized, but the impact of cross input between regions is obvious, and the task of dynamic zeroing in all regions is very arduous. The epidemic situation in Hebei, Jiangsu, Zhejiang, Anhui, Guangdong, Fujian, Liaoning and other provinces tends to be stable on the whole. The epidemic situation in Jilin City, Jilin province continued to improve and was in a downward trend, while the epidemic situation in Changchun showed a downward trend. Recently, the epidemic situation in Shanghai is still high, the risk of community transmission is still high, the prevention and control situation is still severe, and the prevention and control task is still very arduous and urgent.
Since then, from April 19 to 22, there were still more than 2000 newly confirmed cases in China every day. From 0:00 to 24:00 on April 24, 31 provinces (autonomous regions and municipalities directly under the central government) and Xinjiang production and Construction Corps reported 2680 new confirmed cases. There were 2666 local cases (2472 in Shanghai, 79 in Jilin, 26 in Heilongjiang, 14 in Beijing, 14 in Jiangxi, 13 in Zhejiang, 12 in Hunan, 9 in Inner Mongolia, 5 in Henan, 5 in Qinghai, 4 in Jiangsu, 3 in Liaoning, 3 in Guangdong, 2 in Shanxi, 2 in Shandong, 1 in Tianjin, 1 in Fujian and 1 in Sichuan), including 899 cases from asymptomatic infection to confirmed cases (846 in Shanghai, 39 in Jilin, 12 in Zhejiang, 1 in Fujian and 1 in Qinghai). There were 51 new deaths, all local cases, in Shanghai; No new suspected cases.
The current round of epidemic situation is fierce. More than 10000 covid-19 pneumonia cases were added in a single day in Shanghai for the first time on April 4. On the same day, 13354 local covid-19 pneumonia infections were added in Shanghai, including 268 newly diagnosed cases and 13086 asymptomatic infections.
Subsequently, the epidemic situation in Shanghai continued to operate at a high level. As of April 20, more than 400000 people had been infected in this round of epidemic in Shanghai. At the same time, as of 24:00 on April 23, 87 deaths had been reported in Shanghai, including 160 cases of severe and 19 cases of critical. Then, from 0:00 to 24:00 on April 24, 51 new local deaths occurred in Shanghai. At present, the total number of deaths in Shanghai has exceeded 100 in this round of epidemic.
In addition to Shanghai, Jilin, Heilongjiang and other places are also facing the challenge of epidemic prevention and control. At the beginning of March, a new round of epidemic broke out in Jilin Province after the beginning of the year 2022. The number of newly confirmed local cases in a single day increased from single digits to hundreds and then to thousands. After nearly a month’s efforts, the epidemic prevention and control work in Jilin Province has achieved phased results, and the production and living order of residents is gradually restored.
According to the Jilin Health Commission, from 0:00 to 24:00 on April 21, 63 locally confirmed cases were added in the province, including 53 cases in Changchun, 5 cases in Jilin, 4 cases in Yanbian Prefecture and 1 case in Baicheng city; 244 local asymptomatic infections were added, including 211 in Changchun City, 14 in Yanbian Prefecture, 12 in Jilin City, 6 in Baicheng city and 1 in Songyuan City. On April 21, 873 cases of cured and confirmed discharge cases and 1141 cases of asymptomatic infection were added in the province.
At the press conference on epidemic prevention and control in Jilin Province held on the morning of April 21, Geng Jianren, a member of the Party group of Jilin Provincial Health Commission, informed the overall situation of epidemic prevention and control in Jilin Province: at present, the provincial covid-19 pneumonia epidemic prevention and control has achieved phased results, but the epidemic prevention and control situation is still grim. We should continue to adhere to external prevention input and internal prevention rebound, and adhere to the “dynamic zeroing” without hesitation and wavering, Pay close attention to various measures for epidemic prevention and control, and strictly abide by the bottom line of no large-scale rebound of the epidemic.
According to the official website of Heilongjiang Provincial Health Commission, 34 locally confirmed cases of covid-19 pneumonia (all in Harbin) and 56 locally asymptomatic infections (all in Harbin) were added in the province from 0:00 to 24:00 on April 21. As of 24:00 on April 21, there were 304 local confirmed cases and 224 local asymptomatic infections in the province; There are 1 confirmed case imported from abroad and 5 asymptomatic infections imported from abroad.
in the face of the recent situation of multiple, wide-ranging and frequent local epidemic situations in China, China’s epidemic prevention and control adheres to the general policy of “dynamic clearing”
On April 22, Liang Wannian, head of the expert group of the epidemic response and disposal leading group of the National Health Commission and executive vice president of Vanke School of public health and health of Tsinghua University, stressed in an interview with the media that the costs and benefits of adhering to the “dynamic clearing” should be calculated in large accounts, overall accounts and dynamic accounts. Now the cost of “dynamic clearing”, including covid-19 vaccine, nucleic acid detection, shelter construction, human resources and other inputs, is like buying an insurance to deal with risks. In the face of the risks brought by Omicron, China’s insurance has benefited 1.4 billion Chinese people and controlled the Non-Proliferation of the epidemic. In fact, it is to buy insurance for 1.4 billion people. These investments are worth it.
Liang Wannian pointed out that the covid-19 epidemic is far higher than influenza in terms of transmission, pathogenicity and mortality Liang Wannian takes the real-world data of Hong Kong as an example. The average case fatality rate of Omicron epidemic strain in Hong Kong is about 0.75%, seven to eight times that of influenza. From the perspective of the elderly, especially the elderly over the age of 80, its mortality will be nearly 100 times that of ordinary influenza.
another key factor is the covid-19 vaccination rate of the elderly in China
According to the data released by the National Health Commission, as of April 18, the number of vaccinations for the elderly over the age of 60 in China was 225521 million, and 213938 million people had been vaccinated in the whole process. The number of people covered and the number of people vaccinated in the whole process accounted for 85.41% and 81.03% of the elderly population respectively. 154874 million people had been vaccinated.
“China has a huge elderly population, and the vaccination rate of the elderly population is not high enough.” Liang Wannian said that once the epidemic control is relaxed, its outcome can be seen clearly. It must be that the virus is widely spread, and the number of severe cases and deaths among the elderly is huge. It is a great disaster for a country. The emergence of a large number of severe diseases, in turn, runs the medical system, and with the infection of medical personnel, it is bound to cause the demand for normal medical services to be not effectively met, which will form a vicious circle.
2. Sequential booster immunization
“Recently, with the approval of the joint prevention and control mechanism of the State Council, the National Health Commission has begun to deploy sequential immunization.” At the press conference of the joint prevention and control mechanism of the State Council held on February 19, Wu Liangyou, deputy director of the disease control bureau of the National Health Commission, said.
For the concept of “sequential immunization”, Wang Huaqing, chief expert of immunization planning of China CDC, explained that sequential immunization refers to a strategy of vaccination using vaccines with different technical routes at a certain time interval and dose times in order to improve the preventive effect or further reduce the risk of serious adverse reactions.
at the above-mentioned press conference, Wu Liang introduced in detail two schemes of sequential immunization in China:
one is homologous enhanced immunization previously, target people over 18 years old who have been vaccinated with inactivated vaccines of Sinopharm Zhongsheng Beijing company, Wuhan company and Beijing Kexing company, as well as adenovirus vector vaccine of Tianjin Cansino Biologics Inc(688185) company for 6 months can receive one dose of homologous booster immunization, that is, the original vaccine can be used for booster immunization. In addition, the joint prevention and control mechanism of the State Council also approved the homologous enhanced immunization of covid-19 virus inactivated vaccine of Shenzhen Kangtai company and the Institute of biology of Chinese Medical College.
the second is heterologous immunization after the implementation of the sequential booster immunization strategy, the target population who has completed the whole process of vaccination with the above three inactivated vaccines can also choose the recombinant protein vaccine of zhifeilong KOMA or Cansino Biologics Inc(688185) adenovirus vector vaccine for sequential booster immunization.
Wu Liangyou also pointed out that both homologous enhancement and sequential enhancement are implemented among people over the age of 18 who have completed the whole process of vaccination for six months. For the target population, select one of them. The research data show that homologous booster immunization and sequential booster immunization can further improve the immune effect.
In fact, this is not the first time that China has carried out sequential immunization. Wang Huaqing pointed out at the press conference that prior to this, sequential immunization was mainly applied to live attenuated polio vaccine (i.e. “polio sugar pill”), which required four doses in the whole process. The first two doses were inoculated with inactivated trivalent polio vaccine, and the last two doses were inoculated with Bivalent Live Attenuated vaccine.
“For viruses with strong variability and difficult to deal with, sequential immunization is often used.” Shao Yiming, a member of the expert group of the vaccine research and development special class of the scientific research group of the joint prevention and control mechanism of the State Council, explained why it is necessary to carry out sequential immunization at this time. First, different vaccines can complement each other’s advantages. Second, different human qualities may have more side effects on a certain type of vaccine, and vaccination with different technical routes can avoid side effects.
Since the announcement of sequential immunization deployment, people who can carry out sequential booster immunization have attracted much attention. Wang Huaqing said that the following conditions should be met for sequential immunization:
First, the vaccination target is people over the age of 18;
Second, the vaccinated population should complete two doses of inactivated vaccine, and these two doses are covid-19 virus inactivated vaccine of Sinopharm Zhongsheng Beijing company, Beijing Kexing company and Sinopharm Zhongsheng Wuhan company;
Third, the vaccinated objects should complete two doses of vaccination in the whole process, and the interval of sequential immunization should not be less than 6 months;
Fourth, the vaccinated objects have not received booster immunization before sequential booster immunization, that is, they have not received the third injection.
In addition, Wang Huaqing also reminded that personal protection should be done well during vaccination, and their health status should be truthfully reflected to the vaccination doctors. The vaccination doctors should judge whether there are contraindications and whether it is necessary to slow the planting; Stay for 30 minutes after vaccination. In case of adverse reactions suspected to be related to vaccination, if the duration is long and the symptoms are serious, first, report to the vaccination unit and second, seek medical treatment in time.
Since the introduction of the sequential immunization policy, Fujian, Shandong, Hunan, Henan, Chongqing, Chengdu, Xi’an and other places have launched covid-19 vaccine sequential immunization. Before this time, similar deployment and implementation have been made abroad. Wang Huaqing, chief expert of immunization planning of China CDC, pointed out that in some countries in the Americas, Europe and Southeast Asia, sequential immunization has been implemented.
It is reported that the U.S. Food and Drug Administration revised the covid-19 vaccine emergency use authorization on October 20, 2021, allowing vaccinators to choose vaccine booster needles with different brands from those previously vaccinated. The national immunization advisory committee of Canada announced new regulations in June 2021 to allow mixed vaccination of covid-19 vaccine, so as to further accelerate the progress of vaccination.
South Korea, Britain and other countries have launched clinical trials on sequential vaccination of covid-19 vaccine in the first half of 2021.
Shortly after the implementation of sequential vaccination in many countries, based on the existing research data, who issued the interim guidelines for covid-19 vaccine “mixed vaccination” on December 16, 2021 (hereinafter referred to as the “guidelines”). The guidelines suggest that if the first dose is vaccinated with virus vector vaccine, the next dose or booster dose can be vaccinated with messenger RNA (mRNA) vaccine; vice versa. If inactivated vaccine is given at first, virus vector vaccine or mRNA vaccine can be given later.
The who said that based on the safety, immunity and effectiveness of the vaccine, the standard practice is to use the vaccine produced by the same manufacturer throughout the vaccination. However, considering the accessibility of vaccines, vaccines produced by different manufacturers can be used flexibly. However, the who also stressed that only by seriously considering the supply of vaccines and the potential advantages and risks of specific vaccine products can “mixed fighting” be carried out.
3. Who is the next sequential booster vaccine
According to the statistics of 21st Century Business Herald reporter, up to now, seven covid-19 vaccines have been approved for marketing or emergency use in China, including Sinopharm Beijing and Sinopharm Wuhan, Kexing Zhongwei, Shenzhen Kangtai Biological Products Co.Ltd(300601) ( Shenzhen Kangtai Biological Products Co.Ltd(300601) . SZ), inactivated vaccine of Institute of biology of Chinese Medical College, Cansino Biologics Inc(688185) ( Cansino Biologics Inc(688185) . SH) adenovirus vector vaccine, and Chongqing Zhifei Biological Products Co.Ltd(300122) ( Chongqing Zhifei Biological Products Co.Ltd(300122) . SZ) recombinant protein vaccine.
At present, the mainstream covid-19 vaccine in China is inactivated dosage form, and the manufacturers mainly include Sinopharm Beijing, Sinopharm Wuhan, Kexing Zhongwei, Shenzhen Kangtai Biological Products Co.Ltd(300601) , and the Institute of biology of Chinese Medical College. With the sequential strengthening of the approved application, the manufacturer of recombinant protein vaccine Chongqing Zhifei Biological Products Co.Ltd(300122) ( Chongqing Zhifei Biological Products Co.Ltd(300122) . SZ) and the manufacturer of adenovirus vector vaccine Cansino Biologics Inc(688185) ( Cansino Biologics Inc(688185) . SH) will benefit. Meanwhile, the mRNA vaccine of Walvax Biotechnology Co.Ltd(300142) and the recombinant protein vaccine of Livzon Pharmaceutical Group Inc(000513) are still in phase III clinical trials.
31 vaccination prospect of approved sequential Vaccine
On February 19, according to the press conference of the joint prevention and control mechanism of the State Council, after the implementation of the sequential immunization strategy, the target population who has completed the whole process of vaccination with three kinds of inactivated vaccines (Sinopharm Beijing, Sinopharm Wuhan and Kexing Zhongwei inactivated vaccines) can also choose the heavy histone vaccine of zhifeilong KOMA or Cansino Biologics Inc(688185) the adenovirus vector vaccine for sequential immunization. Thus, the recombinant covid-19 protein vaccine (CHO cell) zf2001 of Cansino Biologics Inc(688185) biological adenovirus vector vaccine kweisa and zhifeilong KOMA was officially approved to enter the ranks of sequential booster injections.
31.1 Cansino Biologics Inc(688185) biological keweisha Vaccine
In 2021, Cansino Biologics Inc(688185) , a member of the China Academy of engineering and Chen Wei, a member of the Academy of Sciences, developed the recombinant New Coronavirus vaccine (adenovirus type 5).
Cansino Biologics Inc(688185) official website shows that keweisha adopts one dose vaccination scheme, which can greatly shorten the vaccination cycle, and the vaccine can be stored and transported stably for a long time between 2 ° C and 8 ° C, which can greatly reduce the vaccination management cost. According to the 21st Century Business Herald reporter, at present, the bottleneck of Cansino Biologics Inc(688185) production capacity has been alleviated, and it is expected to increase the shipment scale. Previously, Cansino Biologics Inc(688185) only had a capacity of 200 million doses / year in Tianjin plant; On January 28 this year, Cansino Biologics Inc(688185) located in Baoshan, Shanghai, was put into operation, increasing the production capacity of 200 million doses / year.
In December 2021, the international authoritative medical journal The Lancet published the results of the global multicenter phase III clinical trial of kvisar. The data show that it is safe and effective to vaccinate one dose of clovisa in healthy people aged 18 and above. After 14 days, the severe protection rate was 96.0% and the overall protection rate was 63.7%, which reached the covid-19 vaccine protection rate standard recommended by the World Health Organization, and there was no serious adverse reaction related to the vaccine.
Since Cansino Biologics Inc(688185) the adenovirus vector vaccine has officially become one of the options for sequential immunization Sinolink Securities Co.Ltd(600109) analysis shows that keweisha injection type will carry out homologous and cross sequential vaccination, which will increase the sales in the Chinese market.
According to the paper published on biorxiv in January 2022, the neutralizing antibody level of keweisha against Omicron is 6 times higher than that of inactivated vaccine and 3 times higher than that of recombinant protein vaccine. The previous clinical trial data conducted by Jiangsu CDC showed that the inhaled formulation of keweisha was used for covid-19 cross enhanced vaccination, with excellent safety and immunogenicity. On the 14th and 28th days after the enhancement of inhalation dosage form, the neutralizing antibody level of the subjects was 6.7-10.7 times higher than that of the inactivated homologous enhancement group, respectively.
It is reported that kweisa has accepted the verification of its application for inclusion in the emergency use list (Eul) submitted by the WHO. Combined with the current epidemic situation, if it is included in Eul, Cansino Biologics Inc(688185) the overseas orders of covid-19 vaccine are expected to increase significantly.
31.2 Chongqing Zhifei Biological Products Co.Ltd(300122) recombinant protein covid-19 vaccine “zf2001”
Among the sequential booster vaccines approved this time, the recombinant protein vaccine (CHO cell) zf2001 (hereinafter referred to as “zf2001”) is the first domestic heavy group covid-19 virus protein vaccine approved by zhifeilong Kema, a wholly-owned subsidiary of Chongqing Zhifei Biological Products Co.Ltd(300122) and the Institute of Microbiology of Chinese Academy of Sciences.
As one of the five technical routes of covid-19 vaccine, the vaccine products of recombinant protein route have low requirements for the biosafety level of the production workshop, and have the advantages of high purity, better safety, high yield and low cost.
In March 2021, zf2001 was approved for emergency use by the State Drug Administration and became the fourth covid-19 vaccine approved for emergency use in China; In the same month, the vaccine was registered and listed in Uzbekistan, becoming the first recombinant subunit covid-19 vaccine registered and listed in the world; In February this year, the vaccine was approved as a sequential (heterologous) booster of covid-19 inactivated vaccine. In March 2nd, Chongqing Zhifei Biological Products Co.Ltd(300122) announced that the company was informed from the official website of the State Administration of drug administration that the recombinant New Coronavirus vaccine (CHO cell) was approved for conditional listing and was applicable to prevent the disease caused by COVID-19 virus infection.
Whether approved for marketing or emergency use, it is based on the safety and effectiveness of the vaccine. In August 27, 2021, Chongqing Zhifei Biological Products Co.Ltd(300122) released official data on the international multicenter phase III clinical trial of recombinant New Coronavirus vaccine (CHO cells). The data showed that a total of 221 primary endpoint cases were monitored after the whole course of vaccination, and the protective efficacy of covid-19 for any severity was 81.76%, meeting the effectiveness standard of covid-19 vaccine required by who.
Among them, the protective efficacy of covid-19 for severe and above cases and death cases is 100%. According to the preliminary analysis results after genotyping, the protective effect of the vaccine against alpha mutant was 92.93%; The protective effect on Delta mutant was 77.54%. In terms of safety, there was no significant difference in the overall incidence of adverse events / reactions between the vaccine group and the placebo group, and the safety was good.
32 sequential route of potential covid-19 Vaccine
3.2.1 Livzon Pharmaceutical Group Inc(000513) recombinant protein vaccine
V-01 is an innovative covid-19 recombinant protein vaccine developed by Zhuhai lizuzumab Biotechnology Co., Ltd. (“lizuzumab”), a subsidiary of Livzon Pharmaceutical Group Inc(000513) holding company, in cooperation with the Institute of Biophysics, Chinese Academy of Sciences. It is inoculated in two doses. Its antigen structure is fused with human interferon as a biological adjuvant, which can significantly enhance the level of virus neutralizing antibody and produce effective cell response.
V-01 was approved by the State Food and Drug Administration for clinical trials in early 2021, and then approved to carry out sequential enhanced phase III clinical trials in the Philippines, Pakistan, Russia, Malaysia and other countries. On February 17, Livzon Pharmaceutical Group Inc(000513) ( Livzon Pharmaceutical Group Inc(000513) . SZ) announced that v-01 has completed the interim master data analysis of sequential phase III clinical trials and obtained key data
According to the analysis results of the present analysis, the annual incidence rate of V-01 sequential reinforcement group and two needle inactivated vaccine group were 6.73% and 12.80% respectively, showing significant difference. The absolute protective force of v-01 after sequential strengthening is 61.35%, which has significant effectiveness and has met the WHO standard. In this test, 60 covid-19 virus genotyping and first-generation sequencing of all valid samples are Omicron (the rest are still undergoing second-generation sequencing), indicating that the sequential strengthening of v-01 can produce good protection against covid-19 caused by Omicron infection. At the same time, no safety problems worthy of attention were found.
It is reported that at present, the production of v-01 has realized the localization of raw materials, the supply chain of raw materials is stable and the reserves are sufficient. Based on advanced molecular design, v-01 adjuvant adopts conventional aluminum adjuvant, which gets rid of the dependence of protein vaccines on strong adjuvants with large toxic and side effects and patent monopoly, and helps to promote sustained and stable production capacity release. It is estimated that the production capacity of preparations this year will reach 1.5 billion doses.
For the future market of v-01, Livzon Pharmaceutical Group Inc(000513) responded that although the vaccination rate of covid-19 vaccine in China has been very high and some provinces have successively started to strengthen vaccination, facing the challenge of the continuous spread of the global mutant virus epidemic, the overall national epidemic prevention policy is also actively supporting the accelerated research and development of more technical route vaccines. If Lizhu v-01 is listed in China, it is expected to provide more flexible and scientific options for continuously strengthening immunization in the future and contribute to the fight against the epidemic.
“For the company, income is important, but if our vaccine can play a certain role in fighting the epidemic, social income is more important than enterprise income, which is also our responsibility and responsibility as a pharmaceutical enterprise.” Faced with the balance between commercial interests and social benefits, Livzon Pharmaceutical Group Inc(000513) said.
32.2 clover recombinant protein vaccine
Another potential recombinant protein vaccine enterprise is clover Biology (02197. HK), and its core product is recombinant protein covid-19 vaccine scb-2019 (CPG 1018 / aluminum adjuvant) (hereinafter referred to as “scb-2019”). Scb-2019 is a candidate vaccine of trimeric recombinant protein covid-19. It adopts two doses of vaccination scheme and intramuscular injection. At present, the clinical trial has reached the primary and secondary endpoints of vaccine protective efficacy.
Recently, clover biology announced that on January 21, the Lancet published the final protection effectiveness data of scb-2019. Studies have shown that vaccination with two doses of scb-2019 can provide significant protective efficacy against covid-19 with any severity caused by the variant of recombinant covid-19 virus (sar-cov-2). The protective efficacy of preventing severe and hospitalized covid-19 pneumonia (covid-19) caused by any strain was 100%, the protective efficacy of preventing moderate to severe covid-19 pneumonia caused by any strain was 83.7%, and the protective efficacy of preventing covid-19 pneumonia caused by any strain was 67.2%. In terms of virus variants, the vaccine efficacy of covid-19 to prevent any severity caused by the three main variants was 78.7% (delta variant), 91.8% (gamma variant) and 58.6% (Miao variant), respectively. There were no safety problems during the follow-up of efficacy analysis, and the rate of adverse events was similar in each group.
In the context of sequential strengthening deployment, preliminary data have also been obtained from the heterologous strengthening test of scb-2019. A phase 2 clinical trial in Brazil initially showed that among individuals who had previously received two doses of AstraZeneca vaccine, the neutralizing antibody level of one dose of scb-2019 booster was at least three times higher than that of one dose of AstraZeneca covid-19 booster. In addition, the test data of homology enhancement will be released soon. According to the announcement issued by clover, after the spectra test was revised in January 2022, scb-2019 began to be evaluated as a homologous enhancer. The phase II clinical trial began in Brazil in November 2021, and the preliminary results are expected to be released in the first half of 2022.
In terms of production capacity, the annual output of covid-19 vaccine in clover biological planning reaches 1 billion doses,. The announcement shows that the company under clover biology has signed a long-term vaccine supply agreement with the United Nations Children’s Fund (UNICEF) to provide 414 million doses of scb-2019 vaccine to covax “covid-19 pneumonia vaccine implementation plan” in 2022.
Clover said that it is expected to complete the registration application with the State Food and Drug Administration in mid-2022 and the registration application with the World Health Organization and the European Drug Administration in the third quarter of 2022. Once the conditional approval is obtained, the scb-2019 product will be launched.
33 acceleration of domestic mRNA covid-19 Vaccine
As a new vaccine technology, mRNA vaccine is different from attenuated or inactivated vaccine. MRNA only expresses specific antigens and induces immune response. In addition, it promotes humoral and cellular immune responses and induces the innate immune system. Compared with DNA vaccine, mRNA is safer and more effective, because expression does not need to enter the nucleus, and the probability of random genome integration is almost zero. In addition, mRNA will degrade in a short time (2-3 days) in cells, and the development cycle is short and broad-spectrum. Moreover, the engineering modification of mRNA vaccine can greatly increase its stability and immune efficacy.
Therefore, at present, mRNA covid-19 vaccine has a high degree of international recognition. Many research data also confirmed that mRNA vaccine has more advantages.
Over the past year, the advantages of mRNA vaccine technology route and its outstanding advantages in coping with the global covid-19 epidemic have become the focus of China Meheco Group Co.Ltd(600056) company’s research and development of covid-19 vaccine. Many enterprises began to develop mRNA covid-19 vaccine. From Aibo biology and Aimei vaccine to Shiyao group and Cansino Biologics Inc(688185) , which have obtained clinical trial approval, the momentum of mRNA vaccine research and development in China is rapid.
33.1 Shiyao group and Cansino Biologics Inc(688185) mrna vaccine approved clinical
In from April 3 to 4, 2022, the two mRNA vaccines received the approval documents issued by the State Administration of drugs in succession. They were the New Coronavirus mRNA vaccine developed jointly by the SYS6006 and Cansino Biologics Inc(688185) developed by the Shiyao group and the Precision NanoSystems company of Canada.
The preclinical results of these two mRNA vaccines show that the immune protective effect against the current mainstream mutant strain can more effectively protect the body from the infection of the existing mutant strain. This means that these two new mRNA vaccines can play an important role in fighting Omicron covid-19 pneumonia.
The mRNA COVID-19 vaccine SYS6006 developed by the Shijiazhuang Pharmaceutical Group was independently developed for New Coronavirus variant strain. Its preclinical study shows that the product has good immune protection efficacy against the current main mutation strains including Omicron and Delta. It provides immune protection to the body through humoral immunity and cellular immunity, and can produce memory B cells to provide long-term protective effect.
In addition, Shiyao group also said that the preclinical safety evaluation data also fully proved the safety of the product. The product uses advanced production technology, the process is highly controllable, the consistency between batches is good, and it is easy to realize amplification and industrialization; Moreover, it has good stability and can be stored for a long time between 2 ℃ – 8 ℃. The group has achieved internalized production and domestic substitution of key production raw materials and auxiliary materials of mRNA technology, which can meet the demand of large-scale production capacity supply.
Cansino Biologics Inc(688185) the vaccine developed by also has better protective effect against the existing mutant strains. Its preclinical research results show that the vaccine can induce high titer neutralizing antibodies against a variety of important variants identified by the World Health Organization (who) (including the current epidemic strain Omicron), which has a stronger broad spectrum and can more effectively protect the body from the infection of existing variants.
At the same time, Cansino Biologics Inc(688185) Bio said that it would continue to carry out targeted vaccine research and development in the future by fully relying on the core technology platform including virus vector technology and mRNA technology.
33.2 Aili vaccine mRNA covid-19 vaccine has entered phase II / III clinical trial
The New Coronavirus mRNA vaccine LVRNA009 was independently developed by the Amy vaccine and was approved by the State Food and Drug Administration for clinical trials in March 2021. It is the third domestic mRNA COVID-19 vaccine approved after clinical trials by Abbott bio and microbes. At present, lvrna009 has entered phase II / III clinical trials and has submitted an application for sequential vaccination.
On January 8, 2022, the phase I clinical trial data of Emmy vaccine showed good safety and tolerance results. Lvrna009 all adverse events occurred at level 1-2, and there were no adverse events above level 3; Neither SAE nor solicited adverse events of special concern occurred. During the whole test period, there was no heating above level 3.
Specifically, the test results of live virus neutralizing antibody showed that the geometric mean titer (GMT) of live virus neutralizing antibody of the vaccine was “more than 570 GMT on the 56th day of adult low-dose group, more than 1500 GMT on the 56th day of adult medium dose group and more than 840 GMT on the 56th day of adult high-dose group”. Compared with the phase I clinical trial results of similar products, it shows very good safety and immunogenicity.
In addition to safety and immunogenicity, lvrna009 does not have “harsh” requirements for storage temperature. It is understood that the vaccine can be stored at 2 ℃ ~ 8 ℃ for 1 month and – 20 ℃ for 12 months.
In terms of industrialization, it is reported that Emmy vaccine is currently arranging modular production workshops of mRNA vaccine in many places, and it is planned to carry out the engineering batch production of mRNA covid-19 vaccine in June 2022. In addition, in Shanghai, Beijing and other places, Amy vaccine plans to build new factories, which are expected to be completed by the end of this year and put into operation next year, with an annual production capacity of 400 million doses.
In addition, the AI vaccine also has a New Coronavirus Delta variant mRNA vaccine in the pre clinical stage.
33.3 Walvax Biotechnology Co.Ltd(300142) & Aibo biological phase 3 clinical trial basically ended
MRNA covid-19 vaccine arcov (hereinafter referred to as “arcov”) was jointly developed by the Chinese Academy of Military Medical Sciences (AMMS), Aibo biology and Walvax Biotechnology Co.Ltd(300142) Co., Ltd. at present, phase 1 and phase 2 clinical studies have been completed, phase 3 clinical trials have been basically completed, and relevant data cleaning stage has been entered.
In November 2021, Walvax Biotechnology Co.Ltd(300142) was approved to carry out the sequential vaccination clinical trial of “covid-19 inactivated vaccine + covid-19 mRNA vaccine” for people over 18 years old in Guangxi and Yunnan. At present, the above clinical trials have been completed. On January 24 this year, Lancet microbe, an international authoritative medical journal, published the results of phase I clinical trial of arcov vaccine online. The results showed that arcov was safe and well tolerated at five different doses (5ug, 10ug, 15ug, 20ug and 25ug), and could induce strong humoral and cellular immune responses. Among them, the neutralizing antibody titer induced by 15ug test group was the highest, which was about twice that of convalescent patients with covid-19.
Arcov has high stability and enhanced accessibility, and can remain stable for a long time (at least 6 months) under normal refrigerator temperature (2-8 ℃). In contrast, the mRNA vaccine of Moderna needs to be stored and transported at – 20 ℃ (stable at 2-8 ℃ for 30 days), while Pfizer mRNA vaccine needs to be stored and transported at – 70 ℃ (stable at 2-8 ℃ for 5 days).
However, it is also noteworthy that the incidence of systemic side effects of arcov is 50% – 100%, 15% in phase 3 trials μ The incidence of side effects in g dose group was also as high as 95%.
According to the disclosure of Walvax Biotechnology Co.Ltd(300142) 321, at present, the on-site work of covid-19 mRNA vaccine phase III clinical trial in China has been basically completed, data sorting and continuous serum testing are being carried out, the international multi center phase III clinical trial has also made phased progress, case collection has been carried out, and communication with the local drug administration department has been maintained.
4. Who is expected to win the second half
Due to the early approval for listing, Sinopharm and Sinovac became the beneficiaries of the “first half” of covid-19 vaccine.
Among them, covid-19 virus inactivated vaccines from Sinopharm Beijing and Sinopharm Wuhan were conditionally listed in China on December 30, 2020 and February 25, 2021, respectively. In June 2020, the state approved Kexing covid-19 vaccine for emergency use. On February 5, 2021, the State Food and Drug Administration approved the conditional listing of Kexing covid-19 vaccine in China.
According to the official account of China biological WeChat, as of November 16, 2021, the Chinese medicine has produced nearly 2 billion 500 million doses of COVID-19 vaccine to produce outside China, with an annual capacity exceeding 7 billion doses. So far, China’s biological covid-19 vaccine has been registered and listed in 10 countries around the world, and 112 countries, regions and international organizations have approved emergency use or market access.
In addition to Sinopharm, Kexing Zhongwei is located in the first echelon of covid-19 vaccine. According to the financial report, in the first half of 2021, the sales volume of ZTE Zhongwei was US $11 billion (about 70 billion yuan), and the net profit was US $8.6 billion (about 54 billion yuan).
Its performance soared mainly due to the self-developed covid-19 virus inactivated vaccine coronavac. In addition, according to the financial report disclosed by China biopharmaceutical, its share of the profits of associated companies reached 13.63 billion yuan in 2021, a sharp increase of 47 times year-on-year. The financial report specifically mentioned that the performance of domestic covid-19 vaccine manufacturer Kexing Zhongwei in the associated companies was “particularly outstanding” therefore, according to the shareholding ratio of China biopharmaceutical in ZTE, many investors have calculated that the net profit of ZTE in 2021 may exceed 90 billion yuan
According to Lian Xiaojuan, deputy general manager of ZTE Zhongwei, disclosed publicly on November 18 last year, ZTE Zhongwei has supplied 2.2 billion doses of covid-19 vaccine to the world, of which 1.3 billion doses are supplied to the Chinese market and another 900 million doses are supplied to the international market. On June 1, 2021, covid-19 vaccine of China Kexing was included in the emergency use list of who as of January 29, 2022, Kexing has supplied 2.7 billion doses of covid-19 vaccine to the world, accounting for 23% of the total supply of covid-19 vaccine in the world
At present, the overall annual production capacity of Kexing covid-19 vaccine exceeds 2 billion doses, and has obtained emergency use authorization or conditional listing from 60 countries, regions and international organizations.
However, Chen Zhu, chief analyst of Citic Securities Company Limited(600030) medicine, told the 21st Century Business Herald that the competition for covid-19 vaccine is bound to enter the second half, and the biggest winner is likely to be (Sinopharm) Zhongsheng group, because it has inactivated vaccine, recombinant protein vaccine and MRA vaccine are also entering quickly, which is the “national team” with the most complete variety of vaccines.
With the dividend of covid-19 vaccine, the other three A-share listed companies have to face peer competition while the performance of their products in sales is growing rapidly. According to the newly released performance express, in 2021, Anhui longkema’s parent company Chongqing Zhifei Biological Products Co.Ltd(300122) ( Chongqing Zhifei Biological Products Co.Ltd(300122) . SZ) achieved a revenue of 30.637 billion yuan, a year-on-year increase of 101.68%; The net profit attributable to the parent company was 10.197 billion yuan, a year-on-year increase of 208.88%. According to the proportion of covid-19 vaccine performance contribution in the first half of the year, the company’s annual covid-19 vaccine revenue and net profit were about 11 billion yuan and 7 billion yuan respectively. With the contribution of covid-19 vaccine, Cansino Biologics Inc(688185) Biology ( Cansino Biologics Inc(688185) . SH) also turned losses into profits in one fell swoop. According to the performance report, the revenue in 2021 was nearly 4.3 billion yuan, a year-on-year increase of 171 times, and the net profit was 1.91 billion yuan. According to the annual performance forecast, Shenzhen Kangtai Biological Products Co.Ltd(300601) ( Shenzhen Kangtai Biological Products Co.Ltd(300601) . SZ) has a net profit attributable to the parent company of at least 1.2 billion yuan in 2021, with a maximum year-on-year increase of 106.13%.
However, in the face of factors such as limited production capacity, R & D listing process and fierce market competition, the market share of the three enterprises is still less than that of “pioneers” such as Sinopharm and Kexing.
However, Chen Zhu pointed out that compared with the initial stage of the outbreak, the demand and heat of vaccination must have decreased, but like influenza, there may be a probability of repeated vaccination every year
At present, the covid-19 vaccine market in the first half has been occupied by 89. With the promotion of sequential immunization, China’s later covid-19 vaccine enterprises are speeding up and entering the sequential competition track. However, due to the late “admission”, most of them are still in the stage of clinical trials, and the time when their vaccines are approved for listing is still unknown. In addition, affected by the product pipeline, its own production capacity, peer competition and other factors, it is still worth looking forward to whether it can win in the second half of the covid-19 vaccine battlep align=”center”>
