At the press conference of the joint prevention and control mechanism of the State Council, it was announced last weekend that with the approval of the joint prevention and control mechanism of the State Council, the National Health Commission has begun to deploy the sequential strengthening of immunization. For the target population aged over 18 who have been vaccinated with the inactivated vaccine of Sinopharm Zhongsheng Beijing company, Beijing Kexing company and Sinopharm Zhongsheng Wuhan company for six months, The recombinant protein vaccine of zhifeilongke horse or Cansino Biologics Inc(688185) adenovirus vector vaccine can also be selected for sequential immunization.
After the release of the above news, the reaction of the capital market was relatively calm. When the news came out in advance on February 18, the share prices of Chongqing Zhifei Biological Products Co.Ltd(300122) and Cansino Biologics Inc(688185) only rose slightly. At the opening on February 21, Chongqing Zhifei Biological Products Co.Ltd(300122) opened at 130 yuan / share and closed at 125.61 yuan / share, an increase of only 0.34%. Cansino Biologics Inc(688185) the shares of Hong Kong stocks and science and innovation board opened higher at HK $153 / share and 280 yuan / share respectively, and the closing shares fell to HK $142.2/share and 267.25 yuan / share respectively, with an increase of 1.14% and 1.89% respectively.
In addition to Chongqing Zhifei Biological Products Co.Ltd(300122) and Cansino Biologics Inc(688185) , there are Livzon Pharmaceutical Group Inc(000513) , Walvax Biotechnology Co.Ltd(300142) and other enterprises in the layout of covid-19 vaccine. Industry analysts believe that the third injection of covid-19 vaccine will strengthen the needle market, and the competition among manufacturers will intensify.
Many countries have adopted a sequential strengthening strategy
The so-called sequential reinforcement, namely “heterologous reinforcement”, refers to the interval vaccination of vaccines with different technical routes. Take covid-19 vaccine as an example. If two doses of inactivated vaccine have been vaccinated previously, the vaccine of other non inactivated routes will be used as the booster, that is, sequential booster. Previously, China has been implementing the vaccination strategy of homologous enhanced immunization, that is, the covid-19 vaccine with the same technical route should be selected for vaccination.
Shao Yiming, a member of the expert group of vaccine research and development of the scientific research group of the joint prevention and control mechanism of the State Council, said at the above press conference that according to the previous experience in infectious disease prevention and control, a single vaccine can deal with conventional viruses, but for “cunning and fickle” viruses, different vaccines can be “combined”.
Previously, the World Health Organization also issued interim guidelines for heterologous enhancement of covid-19 vaccine, suggesting that if the first dose is mRNA vaccine, the booster dose can be vaccinated with virus vector vaccine; vice versa. If inactivated vaccine is given at first, virus vector vaccine or mRNA vaccine can be given later. Based on the existing evidence, compared with the homologous vaccination procedure only applicable to inactivated vaccine, heterologous vaccination with vector vaccine or mRNA vaccine shows enhanced immunogenicity, and the level of neutralizing antibody is better than that of inactivated vaccine.
At present, several countries and regions have adopted or recommended “sequential immunization” as an enhancement strategy, including the United Kingdom, the United States, Canada, Chile, Thailand, Brazil, the United Arab Emirates, Peru, Argentina, etc.
Cansino Biologics Inc(688185) , Chongqing Zhifei Biological Products Co.Ltd(300122) took the lead in carrying out relevant research
Cansino Biologics Inc(688185) can be used for sequential enhanced adenovirus vector vaccine (trade name “kvissa”), which is the third generation covid-19 vaccine with adenovirus type 5 as the vector. According to the content released by Cansino Biologics Inc(688185) official wechat on February 19, the results of the clinical study on sequential vaccination of covid-19 vaccine launched by Jiangsu CDC in May 2021 showed that after being strengthened with keweisha, it showed good safety, no serious adverse reactions related to the vaccine were found, and the neutralizing antibody level was five times higher than that of inactivated vaccine, Significantly better than the effect of homologous enhancement. The study also shows that the use of keweisha to strengthen immunity can not only significantly improve the antibody level and prevent the virus from entering the cells, but also improve the cellular immunity and increase the self clearance of infected virus cells.
In addition, the latest sequential strengthening research results jointly published by the Key Laboratory of pathogenic microorganisms and immunology of the Chinese Academy of Sciences, the Institute of Microbiology of the Chinese Academy of Sciences and other cooperative units show that among the subjects who have completed two doses of inactivated vaccine for 4-8 months, covid-19 vaccine with different technical routes has the strongest immune effect, The neutralizing antibody level against the original strain was 7 times higher than that of the recombinant protein vaccine. In addition, the results of this study showed that the use of keweisha to strengthen immunization could provide the strongest protection against Omicron mutant. The level of neutralizing antibody was 6 times higher than that of inactivated vaccine and 3 times higher than that of recombinant protein vaccine.
In addition to the intramuscular dosage form, Cansino Biologics Inc(688185) also developed the adenovirus vector covid-19 vaccine for inhalation, and carried out sequential strengthening related research. The results showed that two doses of inactivated vaccine and one dose of adenovirus vector covid-19 vaccine (inhaled dosage form) could induce very high antibody level and cellular immune response, the level of neutralizing antibody increased by about 300 times, and the level of pseudovirus neutralizing antibody to Omicron variant was 10 times higher than that of three doses of inactivated vaccine.
Chongqing Zhifei Biological Products Co.Ltd(300122) the recombinant protein vaccine (trade name “zhikeweide”) of zhifeilong Kema, a wholly-owned subsidiary, was jointly developed by the Institute of Microbiology of the Chinese Academy of Sciences and Anhui zhifeilong Kema company. The vaccine was registered and listed in Uzbekistan on March 1, 2021, becoming the first recombinant subunit covid-19 vaccine registered and listed in the world, It was approved for emergency use in China on March 10, 2021; Approved for emergency use in Indonesia on October 7, 2021; It was approved for emergency use in Colombia on January 22, 2022.
According to the information released on the official website of zhifeilong Kema on January 28, the recent documents issued by academician Xie Xiaoliang and Professor Zhang Wenhong in cell research show that zhikeweide, as a reinforcing needle of inactivated vaccine, is safe and effective, and can produce higher neutralizing antibodies. The results of Professor Zhang Wenhong’s research in new onset pathogens and infection show that zhikeweide, as a booster needle of inactivated vaccine, also has higher neutralizing antibody titer against Omicron mutant, indicating that it is a very good candidate booster needle.
Approved to strengthen or benefit the company’s performance in sequence
Before being approved for sequential strengthening, covid-19 vaccine has contributed a lot to Chongqing Zhifei Biological Products Co.Ltd(300122) and Cansino Biologics Inc(688185) , and Cansino Biologics Inc(688185) is expected to turn loss into profit in 2021. According to its 2021 performance forecast, the company’s revenue during the reporting period is expected to be 4.2-4.4 billion yuan, with a year-on-year increase of 16773.97% – 17577.49%; The net profit attributable to the parent company is expected to be 1.85 billion yuan – 2 billion yuan.
Up to now, Cansino Biologics Inc(688185) has obtained the emergency use authorization or conditional listing approval granted by more than 10 countries, including China, Pakistan, Mexico, Ecuador, Chile, Argentina, Hungary, Kyrgyzstan, Indonesia and Malaysia, and has been listed in Mexico, Pakistan, Chile, Argentina Malaysia and other countries carried out mass vaccination.
According to the analysis of Southwest Securities Co.Ltd(600369) Research Report, in 2021, Cansino Biologics Inc(688185) covid-19 vaccine will be released in large quantities rapidly, and the overseas export will increase rapidly. Among them, in the fourth quarter of 2021, it is expected to achieve a revenue of 1.11 billion yuan – 1.31 billion yuan, with a significant pre increase year-on-year, which is mainly due to the emergence of Omicron mutant, the surge of overseas epidemic and the large amount of overseas export of covid-19 vaccine. After keweisha was approved for sequential immunization, Cansino Biologics Inc(688185) said that if the relevant national departments increase their procurement, it will have a positive impact on the performance of listed companies.
Chongqing Zhifei Biological Products Co.Ltd(300122) although the contribution of covid-19 vaccine to the performance is not specifically mentioned in the performance report, the data of Chongqing Zhifei Biological Products Co.Ltd(300122) performance express in 2021 shows that during the reporting period, the company’s revenue increased by 101.68% year-on-year and the net profit attributable to the parent increased by 209.22% year-on-year.
For the reason of performance growth, Chongqing Zhifei Biological Products Co.Ltd(300122) only mentioned that the sales of independent products and agent products continued to increase steadily. According to the semi annual report of 2021, the revenue during the reporting period was 13.171 billion yuan, with a year-on-year increase of 88.33%, mainly due to the increase in the sales of independent products. The year-on-year revenue of independent products was RMB 1.467 billion, with a year-on-year increase of RMB 12.26 billion. Zhifeilong Kema, which has covid-19 vaccine, achieved a revenue of 5.313 billion yuan and a net profit of 3.449 billion yuan in the first half of 2021, becoming a subsidiary contributing more than 10% to the net profit of Chongqing Zhifei Biological Products Co.Ltd(300122) . In the Spring Festival message released on the official website of zhifeilong Kema on January 31 this year, it is also mentioned that the sales volume of zhikeweide has exceeded 240 million doses from its emergency use to its supply outside China. On January 10 this year, the vaccine was approved as a sequential booster in Indonesia.
A number of enterprises actively arranged and strengthened in sequence
Tianfeng Securities Co.Ltd(601162) the research report points out that with the strengthening of the third needle market, the competition among enterprises will intensify. Beijing News reporter search found that in addition to Chongqing Zhifei Biological Products Co.Ltd(300122) , Cansino Biologics Inc(688185) , there are other enterprises in the layout.
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. On February 21, the reporter of Beijing News learned that the above clinical trials have been vaccinated.
On January 6 this year, China biology officially announced that the research results published online by biorxiv on January 4 showed that the recombinant protein covid-19 vaccine (nvsi-06-07), developed by Sinopharm Zhongsheng Biotechnology Research Institute / National Engineering Research Center for new vaccines, carried out the phase II randomized, double-blind and controlled clinical trial of “inactivation + recombination” sequential vaccination in China in the UAE, Compared with homologous enhancement of inactivated vaccine, the level of neutralizing antibody against the original strain and variant strains such as delta and Omicron was significantly higher than that of homologous enhancement.
On February 16, Livzon Pharmaceutical Group Inc(000513) also announced that the “recombinant covid-19 virus fusion protein vaccine” (hereinafter referred to as “v-01”) developed by its holding subsidiary Lizhu mAb in cooperation with the Institute of biophysics of the Chinese Academy of Sciences has completed the medium-term master data analysis of the sequential strengthening phase III clinical trial of “2 doses of inactivated vaccine + 1 dose of v-01”. The results show that, The above sequential enhancement scheme has significant strong effectiveness, and can produce good protection against covid-19 infected by Omicron. Previously, the clinical trials of v-01 sequential strengthening scheme have been approved in Pakistan and Malaysia.
